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University of Texas Southwestern Medical Center
1.
Cormier, Kevin William.
Exploration of Chemical and Biochemical Mechanisms of Catalysis.
Degree: 2013, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/1730 
► Nature uses proteins to catalyze a wide range of chemical processes that control cellular signaling. One such enzyme is ERK2 which plays a role in…
(more)
▼ Nature uses proteins to catalyze a wide range of chemical processes that control cellular
signaling. One such enzyme is ERK2 which plays a role in the transmission of signals by catalyzing the phosphorylation of its substrates. The
signaling pathway that it is a part of is important in the control of growth, cell survival and differentiation. As with other proteins, its function is intimately related to its structure, both its activity and selectivity for binding partners affected by its conformation. A mutant of ERK2, discovered in a human oral squamous cell carcinoma cell line, consists of a substitution of a lysine for a glutamic acid residue in the common docking domain (E320K). The effects of this mutation on the structure of ERK2 are examined along with the effect that the conformational change has on protein-protein interactions.
Because of the essential role catalysts play in lowering the activation barriers of otherwise inaccessible reaction pathways, chemists have long looked to nature for inspiration. The functionalization of C–H bonds is one such area of research, where the coveted exploitation of readily available hydrocarbon feedstock is impeded by the stability of the bonds. In this search for potential catalysts, chemists have looked to the metals that act as co-factors for many enzymes. Vanadium, long thought to be at work in halogenation reactions taking place in marine environments, was found to selectively catalyze the oxidation of hydrocarbons at the benzylic position. Understanding the mechanism of a reaction can lead to insights into ways to better harness reactivity and selectivity, something that nature does quite efficiently. In studying the biosynthesis of pyrrole-imidazole alkaloids, a means to mimic nature’s method for the dimerization of oroidin was achieved and the product outcome controlled.
Advisors/Committee Members: Zhang, Xuewu, Goldsmith, Elizabeth J., Tambar, Uttam, Cobb, Melanie H..
Subjects/Keywords: MAP Kinase Signaling System; Pyrroles; Vanadium
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APA (6th Edition):
Cormier, K. W. (2013). Exploration of Chemical and Biochemical Mechanisms of Catalysis. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/1730
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Cormier, Kevin William. “Exploration of Chemical and Biochemical Mechanisms of Catalysis.” 2013. Thesis, University of Texas Southwestern Medical Center. Accessed March 07, 2021.
http://hdl.handle.net/2152.5/1730.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Cormier, Kevin William. “Exploration of Chemical and Biochemical Mechanisms of Catalysis.” 2013. Web. 07 Mar 2021.
Vancouver:
Cormier KW. Exploration of Chemical and Biochemical Mechanisms of Catalysis. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2013. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/2152.5/1730.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Cormier KW. Exploration of Chemical and Biochemical Mechanisms of Catalysis. [Thesis]. University of Texas Southwestern Medical Center; 2013. Available from: http://hdl.handle.net/2152.5/1730
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Texas Southwestern Medical Center
2.
Piala, Alexander Townshend.
Kinetics and Regulation of Protein Kinases.
Degree: 2015, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/4206
► One of the major functions of kinases in biological systems is the relay of signal from an effector to a downstream target. Kinases are regulated…
(more)
▼ One of the major functions of kinases in biological systems is the relay of signal from an effector to a downstream target. Kinases are regulated by a diversity of mechanisms, both internal and external to the
kinase. When the regulation of these kinases is somehow abrogated, disease can result. As such, understanding of these regulatory mechanisms could serve as useful in not only understanding cellular signal propagation, but also the disease states that can arise from their malfunction.
Taking advantage well-developed projects in the Goldsmith lab, three systems were studied: two kinases and one
kinase cascade. The MAP3K Thousand and One
Kinase 2 was the
subject of an inhibitor discovery program using high-throughput screening of a large small-molecule library. Secondly, the mechanism by which the
kinase With No Lysine(K) 1 responds to chloride concentration in order to modulate downstream
signaling was studied. Finally, a cascade comprising the MAP3K Apoptosis
Signaling Kinase 1,
MAP/ERK
Kinase 6, and p38a was studied through modeling approaches using data derived from mass spectrometry.
In each case, mechanisms for regulation were discovered. Tight-binding inhibitors of TAO2 were found that may prove useful in both in in vitro
signaling studies as well as future in vivo work. WNK1 was shown to be regulated by direct chloride binding, which inhibits its auto-phosphorylation and thusly its auto-activation. Finally, important kinetic parameters for MAPK cascade
signaling were determined, and it was demonstrated that additional species outside the cascade do not appear necessary for switch-like behavior under physiological-like in vitro conditions. These diverse regulatory mechanisms showcase how protein kinases manage to synthesize diverse inputs into physiologically meaningful downstream signals.
Advisors/Committee Members: Rosenbaum, Daniel M., Goldsmith, Elizabeth J., Phillips, Margaret A., De Brabander, Jef K..
Subjects/Keywords: Extracellular Signal-Regulated MAP Kinases; MAP Kinase Signaling System; MAP Kinase Kinase Kinases; Signal Transduction
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APA (6th Edition):
Piala, A. T. (2015). Kinetics and Regulation of Protein Kinases. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/4206
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Piala, Alexander Townshend. “Kinetics and Regulation of Protein Kinases.” 2015. Thesis, University of Texas Southwestern Medical Center. Accessed March 07, 2021.
http://hdl.handle.net/2152.5/4206.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Piala, Alexander Townshend. “Kinetics and Regulation of Protein Kinases.” 2015. Web. 07 Mar 2021.
Vancouver:
Piala AT. Kinetics and Regulation of Protein Kinases. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2015. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/2152.5/4206.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Piala AT. Kinetics and Regulation of Protein Kinases. [Thesis]. University of Texas Southwestern Medical Center; 2015. Available from: http://hdl.handle.net/2152.5/4206
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Texas Southwestern Medical Center
3.
Eskiocak, Banu.
Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF Melanoma.
Degree: 2016, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/5733
► Genomic diversity and adaptive plasticity of melanoma tumors limit durable control with conventional and targeted therapies. Nevertheless, pathological activation of the ERK1/2 regulatory system is…
(more)
▼ Genomic diversity and adaptive plasticity of melanoma tumors limit durable control with conventional and targeted therapies. Nevertheless, pathological activation of the ERK1/2 regulatory
system is a linchpin tumorigenic mechanism associated with the majority of both primary and recurrent disease. To avoid common resistance mechanisms associated with perdurance of ERK1/2
signaling, we sought to identify therapeutic targets that are selectively required for tumorigenicity in the presence of pathological ERK1/2
signaling. Such targets could be leveraged in jiu jitsu fashion to breach selective pressure to engage any of the many BRAF-independent ERK1/2 pathway activation mechanisms. By integration of multi-genome chemical and genetic screens; recurrent architectural variants in melanoma tumor genomes; and patient outcome data; we identified 2 mechanistic subtypes of BRAF(V600) melanoma that inform new cancer cell biology and offer new therapeutic opportunities. Subtype membership defines sensitivity to clinical MEK inhibitors versus TBK1/IKBKE inhibitors. Importantly, subtype membership can be predicted using a robust quantitative 5-feature genetic biomarker. This biomarker, or the mechanistic relationships linked to it, can identify a cohort of best responders to clinical MEK inhibitors (detectable in 25% of melanoma patients) and identify a cohort of TBK1/IKBKE inhibitor-sensitive disease among non-responders to current targeted therapy (detectable in 9.9% of melanomas).
Advisors/Committee Members: DeBerardinis, Ralph J., White, Michael A., Brekken, Rolf A., Cobb, Melanie H..
Subjects/Keywords: Biomarkers; DNA Copy Number Variations; MAP Kinase Signaling System; Melanoma; Skin Neoplasms
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APA (6th Edition):
Eskiocak, B. (2016). Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF Melanoma. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/5733
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Eskiocak, Banu. “Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF Melanoma.” 2016. Thesis, University of Texas Southwestern Medical Center. Accessed March 07, 2021.
http://hdl.handle.net/2152.5/5733.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Eskiocak, Banu. “Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF Melanoma.” 2016. Web. 07 Mar 2021.
Vancouver:
Eskiocak B. Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF Melanoma. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2016. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/2152.5/5733.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Eskiocak B. Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF Melanoma. [Thesis]. University of Texas Southwestern Medical Center; 2016. Available from: http://hdl.handle.net/2152.5/5733
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Texas Southwestern Medical Center
4.
Chen, Chiyuan.
Mechanistic Basis of Signal Amplitude Modulation by the Ras Effector IMP.
Degree: 2007, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/593
► The RAF/MEK/MAP Kinase signal transduction cascade is the most extensively studied MAPK pathway that mediates diverse cellular responses to environmental cues, and makes a major…
(more)
▼ The RAF/MEK/
MAP Kinase signal transduction cascade is the most extensively studied MAPK pathway that mediates diverse cellular responses to environmental cues, and makes a major contribution to Ras-dependent oncogenic transformation. The Ras effector and E3 ligase family member IMP (Impedes Mitogenic signal Propagation) acts as a steady-state resistor within the RAFMEK- ERK
kinase module. IMP concentrations are regulated by Ras, through induction of autodegradation, and can modulate signal/response thresholds by directly limiting the assembly of functional KSR1-dependent RAF/MEK complexes. Here, we examine the mechanistic basis of signal amplitude modulation by the Ras effector IMP. We show that the capacity of IMP to inhibit signal propagation through RAF to MEK is a consequence of disrupting assembly of multivalent mitogenic complexes that are required for C-RAF
kinase activation and functional coupling of active kinases to downstream substrates. We also study how Ras regulates IMP functions by isolating IMP mutants compromised for Ras interaction and how post-translational modifications such as sumoylation control IMP activities. Finally, we identify some candidate IMP binding proteins to further investigate how IMP impacts cell behaviors through protein-protein interactions and how IMP is modulated by other proteins.
Advisors/Committee Members: White, Michael A..
Subjects/Keywords: ras Proteins; MAP Kinase Signaling System; Ubiquitin-Protein Ligases
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APA ·
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APA (6th Edition):
Chen, C. (2007). Mechanistic Basis of Signal Amplitude Modulation by the Ras Effector IMP. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/593
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Chen, Chiyuan. “Mechanistic Basis of Signal Amplitude Modulation by the Ras Effector IMP.” 2007. Thesis, University of Texas Southwestern Medical Center. Accessed March 07, 2021.
http://hdl.handle.net/2152.5/593.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Chen, Chiyuan. “Mechanistic Basis of Signal Amplitude Modulation by the Ras Effector IMP.” 2007. Web. 07 Mar 2021.
Vancouver:
Chen C. Mechanistic Basis of Signal Amplitude Modulation by the Ras Effector IMP. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2007. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/2152.5/593.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Chen C. Mechanistic Basis of Signal Amplitude Modulation by the Ras Effector IMP. [Thesis]. University of Texas Southwestern Medical Center; 2007. Available from: http://hdl.handle.net/2152.5/593
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Johannes Gutenberg Universität Mainz
5.
Martin, Anne.
Die funktionelle Rolle von LRP1 in der tPA-vermittelten Aktivierung von NMDA-Rezeptoren.
Degree: 2008, Johannes Gutenberg Universität Mainz
URL: http://ubm.opus.hbz-nrw.de/volltexte/2008/1702/
► Das Low Density Lipoprotein Receptor-related Protein 1 (LRP1) scheint neben seiner ursprünglichen Rolle als Lipoproteinrezeptor auch eine fundamentale Rolle bei der Einleitung von Signaltransduktionskaskaden im…
(more)
▼ Das Low Density Lipoprotein Receptor-related Protein 1 (LRP1) scheint neben seiner ursprünglichen Rolle als Lipoproteinrezeptor auch eine fundamentale Rolle bei der Einleitung von Signaltransduktionskaskaden im sich entwickelnden Gehirn zu spielen. Einer seiner Hauptliganden ist die Serinprotease Tissue-type Plasminogen Aktivator (tPA), welche NMDA-Rezeptor-abhängig MAP Kinasenaktivierung induzieren kann. In dieser Studie sollte daher untersucht werden, ob LRP1 und der NMDA Rezeptor in der tPA-vermittelten Signaltransduktion miteinander kooperieren.
Es konnte gezeigt werden, dass sowohl LRP1 als auch der NMDA Rezeptor an der tPA-induzierten Erk1/2 Phosphorylierung beteiligt sind, da dieser Effekt mit den spezifischen Inhibitoren RAP, MK-801 und DL-AP5 blockiert werden konnte. Eine weitere Bestätigung der LRP1-Spezifität zeigte sich durch shRNA knock-down Experimente. Calcium Imaging Experimente ergaben, dass die Applikation von tPA sowohl in primären, hippokampalen Neuronen als auch in der neuronalen Zelllinie HT22 zu einem robusten Einstrom von Calcium in die Zelle führte, welcher mit dem NMDA Rezeptor Inhibitor MK-801 und dem LRP1 Inhibitor RAP blockiert werden konnte. RNAi Experimente und Überexpressionsstudien bestätigten die Beteiligung von PSD-95 als intrazelluläres Adapterprotein, welches die beiden Rezeptoren miteinander verbindet. Als Bindungsstelle für PSD-95 konnte mit Hilfe von LRP1 knock-in Mausneuronen die distale NPxY(2) Domäne am LRP1 C-Terminus identifiziert werden. Diese Ergebnisse führten zu der Hypothese eines multimeren tPA-LRP1-NMDA Rezeptor Komplexes, der über die primäre Bindung von tPA an LRP1 aktiviert wird und anschließend das Signal an den NMDA Rezeptor weiterleitet. Somit weisen die Ergebnisse dieser Arbeit auf einen neuen, tPA-vermittelten Mechanismus zur Öffnung von Glutamatrezeptoren hin, der eine funktionelle Kooperation von dem Lipoproteinrezeptor LRP1 mit dem NMDA Rezeptor voraussetzt.
The Low Density Lipoprotein Receptor-related Protein 1 (LRP1) emerges to play fundamental roles in cellular signaling pathways in the mammalian brain. One of its prominent ligands is the serine proteinase tissue-type plasminogen activator (tPA), which has been shown to act as a key activator of neuronal MAP kinase pathways via the NMDA receptor. In this study it was set out to examine whether LRP1 and the NMDA receptor might eventually act in a combined fashion to mediate tPA downstream signaling. By blocking tPA from binding to LRP1 using the Receptor-Associated Protein (RAP), and by inhibition of the NMDA receptor with MK-801 or DL-AP5, Erk1/2 activation could be completely inhibited. Further confirmation for the specificity of LRP1 came from shRNA knock-down experiments. Additionally, inhibition of both receptors with MK-801 and RAP resulted in dramatic reduction of tPA-induced calcium influx in primary hippocampal neurons and the neuronal cell line HT22. This indicates a functional interaction between the two receptors. RNAi experiments and overexpression studies confirmed PSD95 as…
Subjects/Keywords: NMDA Rezeptor Aktivierung, LRP1, tPA, MAP Kinase, Calcium Signaling; NMDA receptor activation, LRP1, tPA, MAP Kinase, Calcium signaling; Life sciences
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APA ·
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APA (6th Edition):
Martin, A. (2008). Die funktionelle Rolle von LRP1 in der tPA-vermittelten Aktivierung von NMDA-Rezeptoren. (Doctoral Dissertation). Johannes Gutenberg Universität Mainz. Retrieved from http://ubm.opus.hbz-nrw.de/volltexte/2008/1702/
Chicago Manual of Style (16th Edition):
Martin, Anne. “Die funktionelle Rolle von LRP1 in der tPA-vermittelten Aktivierung von NMDA-Rezeptoren.” 2008. Doctoral Dissertation, Johannes Gutenberg Universität Mainz. Accessed March 07, 2021.
http://ubm.opus.hbz-nrw.de/volltexte/2008/1702/.
MLA Handbook (7th Edition):
Martin, Anne. “Die funktionelle Rolle von LRP1 in der tPA-vermittelten Aktivierung von NMDA-Rezeptoren.” 2008. Web. 07 Mar 2021.
Vancouver:
Martin A. Die funktionelle Rolle von LRP1 in der tPA-vermittelten Aktivierung von NMDA-Rezeptoren. [Internet] [Doctoral dissertation]. Johannes Gutenberg Universität Mainz; 2008. [cited 2021 Mar 07].
Available from: http://ubm.opus.hbz-nrw.de/volltexte/2008/1702/.
Council of Science Editors:
Martin A. Die funktionelle Rolle von LRP1 in der tPA-vermittelten Aktivierung von NMDA-Rezeptoren. [Doctoral Dissertation]. Johannes Gutenberg Universität Mainz; 2008. Available from: http://ubm.opus.hbz-nrw.de/volltexte/2008/1702/
6.
Dandekar, Radhika D.
Regulation of ERK1/2 and SAPK/JNK Phosphorylation by Histamine.
Degree: M.S. in Pharmaceutical Sciences, Pharmaceutical Science (graduate program), 2009, Creighton University
URL: http://hdl.handle.net/10504/4544
► Mitogen activated protein kinases (MAPKs) are specific serine/threonine kinases which respond to various stimuli and control various cellular activities including gene expression, mitosis, cell differentiation,…
(more)
▼ Mitogen activated protein kinases (MAPKs) are specific serine/threonine kinases which respond to various stimuli and control various cellular activities including gene expression, mitosis, cell differentiation, and cell survival/apoptosis. Histamine is implicated in allergic disease and asthma and SAPK/JNK and ERK1/2 are involved in certain aspects of allergic inflammation such as TH2 differentiation and proliferation and apoptosis. This study was designed to investigate the effects of histamine on ERK1/2 and SAPK/JNK phosphorylation in splenocytes.|C57BL/6 splenocytes were treated with different concentrations of histamine (10
-4 M to 10
-11 M). Histamine at higher concentration (10
-4 M) increased ERK2 phosphorylation. There was, however no significant effect seen at other concentrations (10
-6 M - 10
-11 M). Surprisingly, H1 receptor agonist betahistine (10
-5 M), H2 agonist amthamine (10
- 5 M), H3 agonist methimepip (10
-6 M) and H4 agonist 4-methyl histamine (10
-6 M), all increased ERK2 phosphorylation. H1R antagonist pyrilamine (10
-6 M), H2R antagonist ranitidine (10
- 5 M), H3/H4R antagonist thioperamide (10
-6 M), and H3R antagonist clobenpropit (10
-5 M) inhibited histamine mediated ERK2 phosphorylation suggesting that all four histamine receptor subtypes played some role in this phosphorylation. Since TNF-alpha causes phosphorylation of ERK1/2, we investigated whether histamine acted via secretion of TNF-alpha to affect ERK1/2 phosphorylation. As a consequence, TNFalpha knockout mice were used and we found that TNF-alpha was involved in ERK2 phosphorylation. There was complete inhibition of ERK2 phosphorylation by histamine via H2, H3 and H4 agonists, but effects of H1 agonist were inconclusive in TNF-alpha knockout splenocytes. This suggested that histamine indirectly affected the ERK2 phosphorylation via its effects on the secretion of TNF-alpha and H1 receptor played a role in this process.|We performed similar experiments with stress activated protein kinases/c-jun N-terminal kinases (SAPK/JNK). C57BL/6 mice splenocytes were treated with different concentrations of histamine (10
-4 M to 10
-11 M), phorbol 12 myristate 13-acetate (PMA) was used as a positive control and phosphorylation of SAPK/JNK was determined. Histamine inhibited phosphorylation of SAPK/JNK at high concentrations (10
-4 M
-10-8 M) and had no effect on SAPK/JNK phosphorylation at lower concentrations (10
-9 M - 10
- 11 M). Histamine receptor specific agonists were used to identify the histamine receptors involved in the inhibition of SAPK/JNK phosphorylation. H1R agonist betahistine (10-5 M) decreased the phosphorylation of SAPK/JNK. The decrease in SAPK/JNK phosphorylation by histamine was predominantly an H1 receptor effect. H2R agonist amthamine (10
-5 M) did not show any significant effect on SAPK/JNK phosphorylation. H3R agonist…
Advisors/Committee Members: Khan, Manzoor M. (advisor), Dandekar, Radhika D. (cuauthor).
Subjects/Keywords: Histamine – physiology; MAP Kinase Signaling System – drug effects; Phosphorylation – drug effects; Mice, Knockout
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APA ·
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APA (6th Edition):
Dandekar, R. D. (2009). Regulation of ERK1/2 and SAPK/JNK Phosphorylation by Histamine. (Masters Thesis). Creighton University. Retrieved from http://hdl.handle.net/10504/4544
Chicago Manual of Style (16th Edition):
Dandekar, Radhika D. “Regulation of ERK1/2 and SAPK/JNK Phosphorylation by Histamine.” 2009. Masters Thesis, Creighton University. Accessed March 07, 2021.
http://hdl.handle.net/10504/4544.
MLA Handbook (7th Edition):
Dandekar, Radhika D. “Regulation of ERK1/2 and SAPK/JNK Phosphorylation by Histamine.” 2009. Web. 07 Mar 2021.
Vancouver:
Dandekar RD. Regulation of ERK1/2 and SAPK/JNK Phosphorylation by Histamine. [Internet] [Masters thesis]. Creighton University; 2009. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/10504/4544.
Council of Science Editors:
Dandekar RD. Regulation of ERK1/2 and SAPK/JNK Phosphorylation by Histamine. [Masters Thesis]. Creighton University; 2009. Available from: http://hdl.handle.net/10504/4544
7.
Arnette, Donald Ervin, Jr.
Effects of Glucose and Free Fatty Acids on ERK1/2 in Pancreatic B-Cells.
Degree: 2005, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/691
► Diabetes is a growing problem in the United States. There is a growing occurrence of obesity in the United States, which directly adds to the…
(more)
▼ Diabetes is a growing problem in the United States. There is a growing occurrence of obesity in the United States, which directly adds to the incidence and occurrence of diabetes. Our lab has previously showed that the extracellular signal-regulated protein kinases (ERKs) 1 and 2 are activated by elevated concentrations of glucose and are involved in insulin transcription. In this study we examine the mechanism by which glucose induces ERK1/2 activity. The effects of free fatty acids on ERK1/2 activity were also examined. In this study a rat insulinoma cell line was used.
The rat insulinoma cell line INS-1 is a model
system which is commonly used to represent pancreatic ᭣ells. Elevated glucose activates ERK1/2 in INS-1 cells. With the use of several pharmacological agents which interrupt calcium
signaling, it was concluded that calcium
signaling is involved in glucose-induced ERK1/2 activation. Calmodulin and the calmodulin-dependent phosphatase calcineurin were determined to be required for glucose-induced ERK1/2 activity as well as glucagons-like peptide induced ERK1/2 activity. This activation was also shown to require the release of calcium from intracellular stores. It has been well documented that free fatty acids (FFAs) have negative effects on pancreatic ᭣ells. FFAs have been shown to decrease insulin secretion. The effects ofFFAs on ERK1/2 activity were also examined. Chronic exposure of FFAs causes constitutive activation of ERK1/2 in INS-1 cells. This constitutive activity of ERK1/2 was determined to be protein
kinase C (PKC) independent. The FFA-induced ERK1/2 activity resulted in a ERK1/2 nuclear localization pattern that is dramatically different from the usual pattern of ERK1/2 nuclear localization. It has been previously shown that ERK1/2 phosphorylate insulin transcription factors that are required for maximal glucose-induced insulin transcription. This altered ERK1/2 nuclear localization may affect the phosphorylation of these transcription factors, which might explain how chronic exposure to FFAs inhibits insulin transcription.
Advisors/Committee Members: Cobb, Melanie H..
Subjects/Keywords: MAP Kinase Signaling System; Insulinoma; Fatty Acids, Free
…terminal kinase
KRBH
Krebs-Ringer-bicarbonate-HEPES
MAP
mitogen-activated protein
MEK
MAPK… …Lipotoxicity
V.
MAP Kinases and Insulin Gene Transcription
A. Glucose-Induced Insulin Transcription… …glucose-stimulated insulin release from the β-cell.
Figure 1.3
Insulin signaling through the… …acetyl coA carboxylase
ADP
adenosine 5’ diphosphate
AMPK
AMP-activated protein kinase
ATP… …dependent-protein-kinase
CBP
CREB binding protein
CPT1
carnitine-palmitoyl-transferase-1
CRE…
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APA (6th Edition):
Arnette, Donald Ervin, J. (2005). Effects of Glucose and Free Fatty Acids on ERK1/2 in Pancreatic B-Cells. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/691
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Arnette, Donald Ervin, Jr. “Effects of Glucose and Free Fatty Acids on ERK1/2 in Pancreatic B-Cells.” 2005. Thesis, University of Texas Southwestern Medical Center. Accessed March 07, 2021.
http://hdl.handle.net/2152.5/691.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Arnette, Donald Ervin, Jr. “Effects of Glucose and Free Fatty Acids on ERK1/2 in Pancreatic B-Cells.” 2005. Web. 07 Mar 2021.
Vancouver:
Arnette, Donald Ervin J. Effects of Glucose and Free Fatty Acids on ERK1/2 in Pancreatic B-Cells. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2005. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/2152.5/691.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Arnette, Donald Ervin J. Effects of Glucose and Free Fatty Acids on ERK1/2 in Pancreatic B-Cells. [Thesis]. University of Texas Southwestern Medical Center; 2005. Available from: http://hdl.handle.net/2152.5/691
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Georgia
8.
Chappell, James Clyde.
Novel roles for MYC in the maintainence of pluripotency.
Degree: 2015, University of Georgia
URL: http://hdl.handle.net/10724/31398
► Pluripotent stem cells (PSCs) are an important model system for studying early embryonic developmental processes of both normal and diseased organisms. Furthermore, investigating and revealing…
(more)
▼ Pluripotent stem cells (PSCs) are an important model system for studying early embryonic developmental processes of both normal and diseased organisms. Furthermore, investigating and revealing the mechanisms that govern PSC biology will be
fundamental for their eventual use for therapeutic replacement of defective and/or damaged tissues. Examination of the myelocytomatosis oncogene (MYC) family of transcription factors revealed regulation of a set of target genes that are critical for PSC
maintenance, termed the dual-specificity phosphatases (DUSPs). The importance of MYC to PSC biology was previously attributed mainly to its role in activating genes involved in increased metabolism and proliferation. Here I demonstrated that the protein
products of MYC genes activates expression of two DUSP family members, DUSP2 and DUSP7, which consequently inhibit activation of mitogen-activated protein kinase - extracellular signal-regulated kinases (MAPK/ERK) signaling, a key determinant of PSC
differentiation. This finding demonstrates that the significance of MYC in PSC biology is more nuanced than activation of growth promoting genes.
Subjects/Keywords: Stem cells; myc; self-renewal; pluripotency; differentiation; Dusp; Erk; Map kinase signaling
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APA (6th Edition):
Chappell, J. C. (2015). Novel roles for MYC in the maintainence of pluripotency. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/31398
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Chappell, James Clyde. “Novel roles for MYC in the maintainence of pluripotency.” 2015. Thesis, University of Georgia. Accessed March 07, 2021.
http://hdl.handle.net/10724/31398.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Chappell, James Clyde. “Novel roles for MYC in the maintainence of pluripotency.” 2015. Web. 07 Mar 2021.
Vancouver:
Chappell JC. Novel roles for MYC in the maintainence of pluripotency. [Internet] [Thesis]. University of Georgia; 2015. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/10724/31398.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Chappell JC. Novel roles for MYC in the maintainence of pluripotency. [Thesis]. University of Georgia; 2015. Available from: http://hdl.handle.net/10724/31398
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
9.
Carey, Kendall Davis.
Regulation of cell signaling by the small G protein Rap1.
Degree: PhD, 2002, Oregon Health Sciences University
URL: doi:10.6083/M46H4FQ5
;
http://digitalcommons.ohsu.edu/etd/3164
Subjects/Keywords: Mitogen-Activated Protein Kinase Kinases; ras Proteins; MAP Kinase Signaling System; rap1 GTP-Binding Proteins; Jurkat Cells
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Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Carey, K. D. (2002). Regulation of cell signaling by the small G protein Rap1. (Doctoral Dissertation). Oregon Health Sciences University. Retrieved from doi:10.6083/M46H4FQ5 ; http://digitalcommons.ohsu.edu/etd/3164
Chicago Manual of Style (16th Edition):
Carey, Kendall Davis. “Regulation of cell signaling by the small G protein Rap1.” 2002. Doctoral Dissertation, Oregon Health Sciences University. Accessed March 07, 2021.
doi:10.6083/M46H4FQ5 ; http://digitalcommons.ohsu.edu/etd/3164.
MLA Handbook (7th Edition):
Carey, Kendall Davis. “Regulation of cell signaling by the small G protein Rap1.” 2002. Web. 07 Mar 2021.
Vancouver:
Carey KD. Regulation of cell signaling by the small G protein Rap1. [Internet] [Doctoral dissertation]. Oregon Health Sciences University; 2002. [cited 2021 Mar 07].
Available from: doi:10.6083/M46H4FQ5 ; http://digitalcommons.ohsu.edu/etd/3164.
Council of Science Editors:
Carey KD. Regulation of cell signaling by the small G protein Rap1. [Doctoral Dissertation]. Oregon Health Sciences University; 2002. Available from: doi:10.6083/M46H4FQ5 ; http://digitalcommons.ohsu.edu/etd/3164
University of Manchester
10.
Kowalczyk, Katarzyna.
Cell division control in the changing
environment.
Degree: 2014, University of Manchester
URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:241611
► Cell growth and cell cycle progression are tightly controlled in order to provide optimal proliferation in a particular environment. The activities of multiple signalling pathways…
(more)
▼ Cell growth and cell cycle progression are tightly
controlled in order to provide optimal proliferation in a
particular environment. The activities of multiple signalling
pathways are a prerequisite for the progression through the cell
cycle and for the increase in cell number. These activities need to
be constantly monitored and adjusted to the particular conditions
such as nutrient availability or exposure to stress. Failure to
properly regulate key signalling pathways could be fatal leading to
cell death. This study aims to enhance our understanding of how
endogenous inhibitors of the two main signalling pathways, the
stress
MAP kinase and TOR pathways, are controlled and how these
controls are translated into target/substrate activity. The first
part of the study is dedicated to analysis of Pyp2, a Sty1 MAPK
phosphatase. Pyp2 and Pyp1 are both tyrosine specific phosphatases
and are responsible for Sty1 inactivation. Despite the high degree
of similarity between these molecules, in particular conditions
cells depend only on proper Pyp2 and not Pyp1 regulation. A
combination of biological and biochemical tools with additional
help from bioinformatics allowed the identification of a key
regulatory “domain” present only in Pyp2, the linker region. This
region is subjected to Sty1-dependent phosphorylation, which in
turn increases Pyp2 stability. Detailed linker region analysis
suggests that Sty1 has the possibility to auto-regulate through
control of Pyp2 protein stability. The second part of this study
aims to characterise what appears to be a novel inhibitor of TOR
signalling. Two independent screens set to find new regulators of
TOR signalling identified the Ppk32
kinase as a potential new
regulator in the TOR pathway. A further characterisation indicates
that Ppk32 can significantly reduce TOR activity and eventually
block cell growth. Altered traffic through the endomembrane systems
in the absence of Ppk32 suggests that this molecule may directly or
indirectly alter TOR signalling via an effect on internal
membranes.
Advisors/Committee Members: TAYLOR, STEPHEN S, Taylor, Stephen, Petersen, Janni.
Subjects/Keywords: MAP kinase; TOR kinase
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kowalczyk, K. (2014). Cell division control in the changing
environment. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:241611
Chicago Manual of Style (16th Edition):
Kowalczyk, Katarzyna. “Cell division control in the changing
environment.” 2014. Doctoral Dissertation, University of Manchester. Accessed March 07, 2021.
http://www.manchester.ac.uk/escholar/uk-ac-man-scw:241611.
MLA Handbook (7th Edition):
Kowalczyk, Katarzyna. “Cell division control in the changing
environment.” 2014. Web. 07 Mar 2021.
Vancouver:
Kowalczyk K. Cell division control in the changing
environment. [Internet] [Doctoral dissertation]. University of Manchester; 2014. [cited 2021 Mar 07].
Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:241611.
Council of Science Editors:
Kowalczyk K. Cell division control in the changing
environment. [Doctoral Dissertation]. University of Manchester; 2014. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:241611
University of Manchester
11.
Kowalczyk, Katarzyna.
Cell division control in the changing environment.
Degree: PhD, 2015, University of Manchester
URL: https://www.research.manchester.ac.uk/portal/en/theses/cell-division-control-in-the-changing-environment(32559133-4156-4844-b1c5-a5afe678b4df).html
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799229
► Cell growth and cell cycle progression are tightly controlled in order to provide optimal proliferation in a particular environment. The activities of multiple signalling pathways…
(more)
▼ Cell growth and cell cycle progression are tightly controlled in order to provide optimal proliferation in a particular environment. The activities of multiple signalling pathways are a prerequisite for the progression through the cell cycle and for the increase in cell number. These activities need to be constantly monitored and adjusted to the particular conditions such as nutrient availability or exposure to stress. Failure to properly regulate key signalling pathways could be fatal leading to cell death. This study aims to enhance our understanding of how endogenous inhibitors of the two main signalling pathways, the stress MAP kinase and TOR pathways, are controlled and how these controls are translated into target/substrate activity. The first part of the study is dedicated to analysis of Pyp2, a Sty1 MAPK phosphatase. Pyp2 and Pyp1 are both tyrosine specific phosphatases and are responsible for Sty1 inactivation. Despite the high degree of similarity between these molecules, in particular conditions cells depend only on proper Pyp2 and not Pyp1 regulation. A combination of biological and biochemical tools with additional help from bioinformatics allowed the identification of a key regulatory "domain" present only in Pyp2, the linker region. This region is subjected to Sty1-dependent phosphorylation, which in turn increases Pyp2 stability. Detailed linker region analysis suggests that Sty1 has the possibility to auto-regulate through control of Pyp2 protein stability. The second part of this study aims to characterise what appears to be a novel inhibitor of TOR signalling. Two independent screens set to find new regulators of TOR signalling identified the Ppk32 kinase as a potential new regulator in the TOR pathway. A further characterisation indicates that Ppk32 can significantly reduce TOR activity and eventually block cell growth. Altered traffic through the endomembrane systems in the absence of Ppk32 suggests that this molecule may directly or indirectly alter TOR signalling via an effect on internal membranes.
Subjects/Keywords: MAP kinase; TOR kinase
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kowalczyk, K. (2015). Cell division control in the changing environment. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/cell-division-control-in-the-changing-environment(32559133-4156-4844-b1c5-a5afe678b4df).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799229
Chicago Manual of Style (16th Edition):
Kowalczyk, Katarzyna. “Cell division control in the changing environment.” 2015. Doctoral Dissertation, University of Manchester. Accessed March 07, 2021.
https://www.research.manchester.ac.uk/portal/en/theses/cell-division-control-in-the-changing-environment(32559133-4156-4844-b1c5-a5afe678b4df).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799229.
MLA Handbook (7th Edition):
Kowalczyk, Katarzyna. “Cell division control in the changing environment.” 2015. Web. 07 Mar 2021.
Vancouver:
Kowalczyk K. Cell division control in the changing environment. [Internet] [Doctoral dissertation]. University of Manchester; 2015. [cited 2021 Mar 07].
Available from: https://www.research.manchester.ac.uk/portal/en/theses/cell-division-control-in-the-changing-environment(32559133-4156-4844-b1c5-a5afe678b4df).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799229.
Council of Science Editors:
Kowalczyk K. Cell division control in the changing environment. [Doctoral Dissertation]. University of Manchester; 2015. Available from: https://www.research.manchester.ac.uk/portal/en/theses/cell-division-control-in-the-changing-environment(32559133-4156-4844-b1c5-a5afe678b4df).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799229
12.
Yang, Youfeng.
The Role Of Map Kinase Cascade In Msp Signaling Response.
Degree: PhD, 2010, University of Alabama – Birmingham
URL: http://contentdm.mhsl.uab.edu/u?/etd,1399
► The MSP domain is an evolutionarily conserved immunoglobulin-like structure of about 120 amino acids (Miller et al., 2001). A P56S missense mutation in the MSP…
(more)
▼ The MSP domain is an evolutionarily conserved immunoglobulin-like structure of about 120 amino acids (Miller et al., 2001). A P56S missense mutation in the MSP domain of the human vapb gene is associated with a dominantly inherited form of Amyotropic Lateral Sclerosis (ALS) or Spinal Muscular Atrophy (SMA) (Nishimura et al., 2004). In C. elegans, secreted MSP binds to the VAB-1 Eph receptor and other receptors on oocyte and ovarian sheath cell surfaces (Miller et al., 2003). We have recently shown that the P56S mutation prevents secretion of the VAPB MSP domain, suggesting that the signaling function is important in ALS and SMA pathogenesis (Tsuda et al., 2008).Secreted MSPs bind to multiple receptors on oocyte and ovarian sheath cells to stimulate oocyte MPK-1 ERK MAP Kinase (MAPK) phosphorylation, but the function and mechanism of this phosphorylation event is not well understood. Here we show that the Shp class protein-tyrosine phosphatase PTP-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote MSP-induced MPK-1 phosphorylation. PTP-2 inhibits multiple RasGAPs, resulting in sustained Ras activation necessary for high oocyte maturation rates. We also provide evidence that MSP promotes production of reactive oxygen species (ROS) to augment MPK-1 phosphorylation. The Cu/Zn superoxide dismutase SOD-1 inhibits MPK-1 phosphorylation downstream of, or in parallel to ptp-2. Our results support the model that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation. The C. elegans vapb homolog VPR-1 (VAP Related) is required for wild type motility and body wall muscle mitochondrial function. We have investigated mutations in ptp-2 and let-60 Ras, which cause defects in mitochondrial shape due to abnormal fission and fusion (dynamics). These experiments help us delineate a signaling pathway that regulates mitochondrial function.This dissertation elaborates the signaling function of the MSP domain in oocyte maturation and muscle mitochondrial dynamics and may provide insight into the molecular mechanisms behind ALS and SMA. Moreover, VAP MSP domains are ligands for Eph receptors, the most abundant class of receptor tyrosine kinases in the human genome. Thus, these studies may be of broad significance.
PhD
1 online resource (xiv, 111 p.) :ill., digital, PDF file.
Cell Biology
Joint Health Sciences
Major Sperm Protein Signaling MAP Kinase pathway
UNRESTRICTED
Advisors/Committee Members: MICHAEL A. MILLER, YODER,BRADLEY CHANG,CHENBEI MARQUES,GUILLERMO SERRA,ROSA LIN,WEEI-CHIN.
Subjects/Keywords: Caenorhabditis elegans – metabolism.<; br>; Helminth Proteins – physiology.<; br>; MAP Kinase Signaling System – physiology.<; br>; Mitogen-Activated Protein Kinases – metabolism.<; br>; Oocytes – physiology<; br>; Reactive Oxygen Species – metabolism<; br>; Signal Transduction – physiology
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APA ·
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Manager
APA (6th Edition):
Yang, Y. (2010). The Role Of Map Kinase Cascade In Msp Signaling Response. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,1399
Chicago Manual of Style (16th Edition):
Yang, Youfeng. “The Role Of Map Kinase Cascade In Msp Signaling Response.” 2010. Doctoral Dissertation, University of Alabama – Birmingham. Accessed March 07, 2021.
http://contentdm.mhsl.uab.edu/u?/etd,1399.
MLA Handbook (7th Edition):
Yang, Youfeng. “The Role Of Map Kinase Cascade In Msp Signaling Response.” 2010. Web. 07 Mar 2021.
Vancouver:
Yang Y. The Role Of Map Kinase Cascade In Msp Signaling Response. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2010. [cited 2021 Mar 07].
Available from: http://contentdm.mhsl.uab.edu/u?/etd,1399.
Council of Science Editors:
Yang Y. The Role Of Map Kinase Cascade In Msp Signaling Response. [Doctoral Dissertation]. University of Alabama – Birmingham; 2010. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1399
13.
Wang, Mengxi.
Role of Map4k4 in Skeletal Muscle Differentiation: A Dissertation.
Degree: Interdisciplinary Graduate Program, Program in Molecular Medicine, 2013, U of Massachusetts : Med
URL: http://escholarship.umassmed.edu/gsbs_diss/675
► Skeletal muscle is a complicated and heterogeneous striated muscle tissue that serves critical mechanical and metabolic functions in the organism. The process of generating…
(more)
▼ Skeletal muscle is a complicated and heterogeneous striated muscle tissue that serves critical mechanical and metabolic functions in the organism. The process of generating skeletal muscle, myogenesis, is elaborately coordinated by members of the protein
kinase family, which transmit diverse signals initiated by extracellular stimuli to myogenic transcriptional hierarchy in muscle cells. Mitogen-activated protein kinases (MAPKs) including p38 MAPK, c-Jun N terminal
kinase (JNK) and extracellular signal-regulated protein
kinase (ERK) are components of serine/threonine protein
kinase cascades that play important roles in skeletal muscle differentiation. The exploration of MAPK upstream kinases identified mitogen activated protein
kinase kinase
kinase kinase 4 (MAP4K4), a serine/threonine protein
kinase that modulates p38 MAPK, JNK and ERK activities in multiple cell lines. Our lab further discovered that Map4k4 regulates peroxisome proliferator-activated receptor γ (PPARγ) translation in cultured adipocytes through inactivating mammalian target of rapamycin (mTOR), which controls skeletal muscle differentiation and hypotrophy in
kinase-dependent and -independent manners. These findings suggest potential involvement of Map4k4 in skeletal myogenesis.
Therefore, for the first part of my thesis, I characterize the role of Map4k4 in skeletal muscle differentiation in cultured muscle cells. Here I show that Map4k4 functions as a myogenic suppressor mainly at the early stage of skeletal myogenesis with a moderate effect on myoblast fusion during late-stage muscle differentiation. In agreement, Map4k4 expression and protein
kinase activity are declined with myogenic differentiation. The inhibitory effect of Map4k4 on skeletal myogenesis requires its
kinase activity. Surprisingly, none of the identified Map4k4 downstream effectors including p38 MAPK, JNK and ERK is involved in the Map4k4-mediated myogenic differentiation. Instead, expression of myogenic regulatory factor Myf5, a positive mediator of skeletal muscle differentiation is transiently regulated by Map4k4 to partially control skeletal myogenesis. Mechanisms by which Map4k4 modulates Myf5 amount have yet to be determined.
In the second part of my thesis, I assess the relationship between Map4k4 and IGF-mediated
signaling pathways. Although siRNA-mediated silencing of Map4k4 results in markedly enhanced myotube formation that is identical to the IGF-induced muscle hypertrophic phenotype, and Map4k4 regulates IGF/Akt
signaling downstream effector mTOR in cultured adipocytes, Map4k4 appears not to be involved in the IGF-mediated ERK1/2
signaling axis and the IGF-mediated Akt
signaling axis in C2C12 myoblasts. Furthermore, Map4k4 does not affect endogenous Akt
signaling or mTOR activity during C2C12 myogenic differentiation.
The results presented here not only identify Map4k4 as a novel suppressor of skeletal muscle differentiation, but also add to our knowledge of Map4k4 action on multiple
signaling pathways in muscle cells during skeletal…
Advisors/Committee Members: Michael Czech, PhD.
Subjects/Keywords: Cell Differentiation; Cell Line; Developmental Gene Expression Regulation; MAP Kinase Signaling System; Muscle Development; Skeletal Muscle Fibers; Myoblasts; Myogenic Regulatory Factor 5; Protein-Serine-Threonine Kinases; RNA Interference; Small Interfering RNA; Up-Regulation; Cell Biology; Developmental Biology; Molecular Biology; Molecular Genetics
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wang, M. (2013). Role of Map4k4 in Skeletal Muscle Differentiation: A Dissertation. (Doctoral Dissertation). U of Massachusetts : Med. Retrieved from http://escholarship.umassmed.edu/gsbs_diss/675
Chicago Manual of Style (16th Edition):
Wang, Mengxi. “Role of Map4k4 in Skeletal Muscle Differentiation: A Dissertation.” 2013. Doctoral Dissertation, U of Massachusetts : Med. Accessed March 07, 2021.
http://escholarship.umassmed.edu/gsbs_diss/675.
MLA Handbook (7th Edition):
Wang, Mengxi. “Role of Map4k4 in Skeletal Muscle Differentiation: A Dissertation.” 2013. Web. 07 Mar 2021.
Vancouver:
Wang M. Role of Map4k4 in Skeletal Muscle Differentiation: A Dissertation. [Internet] [Doctoral dissertation]. U of Massachusetts : Med; 2013. [cited 2021 Mar 07].
Available from: http://escholarship.umassmed.edu/gsbs_diss/675.
Council of Science Editors:
Wang M. Role of Map4k4 in Skeletal Muscle Differentiation: A Dissertation. [Doctoral Dissertation]. U of Massachusetts : Med; 2013. Available from: http://escholarship.umassmed.edu/gsbs_diss/675
14.
De Zutter, Gerard S.
Stress Activated Protein Kinase Regulation of Gene Expression in Apoptotic Neurons: A Dissertation.
Degree: Interdisciplinary Graduate Program, Program in Molecular Medicine, 2001, U of Massachusetts : Med
URL: https://escholarship.umassmed.edu/gsbs_diss/168
► Summary Basic biological processes require gene expression. Tightly regulated molecules known as transcription factors mediate the expression of genes in development and disease. Signal…
(more)
▼ Summary
Basic biological processes require gene expression. Tightly regulated molecules known as transcription factors mediate the expression of genes in development and disease. Signal transduction pathways, which respond to environmental cues or stressors are major regulators of the transcription factors. Use of macromolecular synthesis inhibitors in models of normal neurodevelopment and neurodegenerative cell death has led to the discovery that gene expression is required for these processes to occur (Martin et. al.,(1988),
J Cell Biol 106p829). To date, however, the identities of very few of the genes required in these events have been revealed. Hence, the activation or requirement of specific
signaling pathways leading to the expression of known apoptotic genes is not well established. Utilizing the neurothrophic factor deprivation and neurotoxin models of programmed cell death we address these gaps in our understanding of the molecular mechanism of apoptosis as it occurs in neuronal cell death.
Nerve growth factor (NGF) withdrawal from PC12 cells leads to the activation of p38 and apoptosis. The functional significance of 38 activation in this paradigm of cell death is not known. To increase our understanding of apoptosis I examined the requirement for p38 activity in pro-apoptotic gene expression in PC12 cells. I performed a subtractive hybridization that led to the identification of the monoamine oxidase (MAG) gene as induced in response to NGF withdrawal. Using the p38 inhibitor PD169316 I showed that the NGF withdrawal stimulated induction of the MAG gene and apoptosis is blocked by inhibition of the p38
MAP kinase pathway. I also determined that the MAG inhibitor clorgyline blocked cell death indicating that MAG activity contributes to the cell death caused by NGF withdrawal. Together, these data indicate that the p38
MAP kinase pathway targets the MAG gene in response to apoptotic stimuli.
To study the requirement for the JNK
signaling pathway in neurodegeneration I stimulated primary cortical neurons with the neurotoxin arsenite. Arsenite treatment of primary neurons leads to both JNK and p38 activation and subsequently apoptosis. Utilizing transgenic mice lacking the JNK3 gene I demonstrated that JNK3 specifically contributes to the effects of arsenite in these cells. Ribonuclease protection assays were used to identify Fas ligand as a molecule whose arsenite-induced expression is dependent on the JNK3 signal transduction pathway. Furthermore, I have shown that neurons deficient in
signaling mediated by the receptor for Fas ligand are resistant to cell death due to arsenite treatment. These results in total have established that the JNK3 mediated expression of Fas ligand contributes to the arsenite induced death of cortical neurons.
In summary, the work presented in these studies identifies the JNK and p38
MAP kinase signal transduction pathways as mediators of apoptosis in neuronal cells. Importantly, I have provided evidence…
Advisors/Committee Members: Roger J. Davis, Ph.D..
Subjects/Keywords: MAP Kinase Signaling System; Gene Expression; Protein Kinases; Apoptosis; Cells; Enzymes and Coenzymes; Genetic Phenomena; Investigative Techniques
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APA ·
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MLA ·
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Manager
APA (6th Edition):
De Zutter, G. S. (2001). Stress Activated Protein Kinase Regulation of Gene Expression in Apoptotic Neurons: A Dissertation. (Doctoral Dissertation). U of Massachusetts : Med. Retrieved from https://escholarship.umassmed.edu/gsbs_diss/168
Chicago Manual of Style (16th Edition):
De Zutter, Gerard S. “Stress Activated Protein Kinase Regulation of Gene Expression in Apoptotic Neurons: A Dissertation.” 2001. Doctoral Dissertation, U of Massachusetts : Med. Accessed March 07, 2021.
https://escholarship.umassmed.edu/gsbs_diss/168.
MLA Handbook (7th Edition):
De Zutter, Gerard S. “Stress Activated Protein Kinase Regulation of Gene Expression in Apoptotic Neurons: A Dissertation.” 2001. Web. 07 Mar 2021.
Vancouver:
De Zutter GS. Stress Activated Protein Kinase Regulation of Gene Expression in Apoptotic Neurons: A Dissertation. [Internet] [Doctoral dissertation]. U of Massachusetts : Med; 2001. [cited 2021 Mar 07].
Available from: https://escholarship.umassmed.edu/gsbs_diss/168.
Council of Science Editors:
De Zutter GS. Stress Activated Protein Kinase Regulation of Gene Expression in Apoptotic Neurons: A Dissertation. [Doctoral Dissertation]. U of Massachusetts : Med; 2001. Available from: https://escholarship.umassmed.edu/gsbs_diss/168
15.
Ramo, Kasmir.
Jun Kinases in Hematopoiesis, and Vascular Development and Function: A Dissertation.
Degree: PhD, Program in Molecular Medicine, 2015, U of Massachusetts : Med
URL: https://escholarship.umassmed.edu/gsbs_diss/789
► Arterial occlusive diseases are major causes of morbidity and mortality in industrialized countries and represent a huge economic burden. The extent of the native…
(more)
▼ Arterial occlusive diseases are major causes of morbidity and mortality in industrialized countries and represent a huge economic burden. The extent of the native collateral circulation is an important determinant of blood perfusion restoration and therefore the severity of tissue damage and functional impairment that ensues following arterial occlusion. Understanding the mechanisms responsible for collateral artery development may provide avenues for therapeutic intervention. Here, we identify a critical requirement for mixed lineage
kinase (MLK) – cJun-NH2-terminal
kinase (JNK)
signaling in vascular morphogenesis and native collateral artery development. We demonstrate that Mlk2-/-Mlk3-/- mice or mice with compound JNK-deficiency in the vascular endothelium display abnormal collateral arteries, which are unable to restore blood perfusion following arterial occlusion, leading to severe tissue necrosis in animal models of femoral and coronary artery occlusion. Employing constitutive and inducible conditional deletion strategies, we demonstrate that endothelial JNK acts during the embryonic development of collateral arteries to ensure proper patterning and maturation, but is dispensable for angiogenic and arteriogenic responses in adult mice. During developmental vascular morphogenesis, MLK – JNK
signaling is required for suppression of excessive sprouting angiogenesis likely via JNK-dependent regulation of Dll4 expression and Notch
signaling. This function of JNK may underlie its critical requirement for native collateral artery formation. Thus, this study introduces MLK – JNK
signaling as a major regulator of vascular development.
In contrast, we find that JNK in hematopoietic cells, which are thought to share a common mesodermally-derived precursor with endothelial cells, is cellautonomously dispensable for normal hematopoietic development and hematopoietic stem cell self-renewal, illustrating the highly context dependent function of JNK.
Advisors/Committee Members: Roger J. Davis, PhD.
Subjects/Keywords: Arterial Occlusive Diseases; Collateral Circulation; Endothelial Cells; Vascular Endothelium; Hematopoietic Stem Cells; Hematopoiesis; MAP Kinase Signaling System; JNK Mitogen-Activated Protein Kinases; Cardiology; Cardiovascular Diseases; Cell Biology; Cellular and Molecular Physiology; Developmental Biology
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APA (6th Edition):
Ramo, K. (2015). Jun Kinases in Hematopoiesis, and Vascular Development and Function: A Dissertation. (Doctoral Dissertation). U of Massachusetts : Med. Retrieved from https://escholarship.umassmed.edu/gsbs_diss/789
Chicago Manual of Style (16th Edition):
Ramo, Kasmir. “Jun Kinases in Hematopoiesis, and Vascular Development and Function: A Dissertation.” 2015. Doctoral Dissertation, U of Massachusetts : Med. Accessed March 07, 2021.
https://escholarship.umassmed.edu/gsbs_diss/789.
MLA Handbook (7th Edition):
Ramo, Kasmir. “Jun Kinases in Hematopoiesis, and Vascular Development and Function: A Dissertation.” 2015. Web. 07 Mar 2021.
Vancouver:
Ramo K. Jun Kinases in Hematopoiesis, and Vascular Development and Function: A Dissertation. [Internet] [Doctoral dissertation]. U of Massachusetts : Med; 2015. [cited 2021 Mar 07].
Available from: https://escholarship.umassmed.edu/gsbs_diss/789.
Council of Science Editors:
Ramo K. Jun Kinases in Hematopoiesis, and Vascular Development and Function: A Dissertation. [Doctoral Dissertation]. U of Massachusetts : Med; 2015. Available from: https://escholarship.umassmed.edu/gsbs_diss/789
University of Toronto
16.
Yuen, Stella Lai Yee.
The Role of the Coxsackie-adenovirus Receptor in the Pathogenesis of Heart Disease and Coxsackieviral Myocarditis.
Degree: 2010, University of Toronto
URL: http://hdl.handle.net/1807/24657
► The coxsackie-adenovirus receptor (CAR) is a viral receptor for Group B coxsackieviruses (CVB). Physiologically, CAR is a cellular adhesion protein. I report that upregulation of…
(more)
▼ The coxsackie-adenovirus receptor (CAR) is a viral receptor for Group B coxsackieviruses (CVB). Physiologically, CAR is a cellular adhesion protein. I report that upregulation of cardiac CAR in the young adult mouse (CAR+/MtTA+ ) caused a cardiomyopathy that was characterized by inflammation and hypertrophy. In the hearts of CAR+/MtTA+ mice c-Jun N terminal kinase (JNK) was specifically activated. JNK activation is known to promote hypertrophy of cardiomyocytes, and disrupt proteins at the intercalated disc. CVB3-infected CAR+/MtTA+ mice did not exhibit increased cardiac viral load or myocarditis severity, but did demonstrate a greater cardiac interferon-γ (IFN-γ) response when compared to littermate controls. CAR-induced expression of this antiviral cytokine may have prevented the increase in myocarditis susceptibility. Further investigation into the activation of protein kinase signaling, and antiviral signaling will provide better understanding of how CAR participates in the pathogenesis of both viral and non-viral heart diseases.
MAST
Advisors/Committee Members: Opavsky, Mary Anne, Medical Science.
Subjects/Keywords: immunology; virology; cardiomyopathy; coxsackie-adenovirus receptor; innate immunity; coxsackievirus B; MAP kinase signaling; 0307; 0379; 0720; 0306
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APA (6th Edition):
Yuen, S. L. Y. (2010). The Role of the Coxsackie-adenovirus Receptor in the Pathogenesis of Heart Disease and Coxsackieviral Myocarditis. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/24657
Chicago Manual of Style (16th Edition):
Yuen, Stella Lai Yee. “The Role of the Coxsackie-adenovirus Receptor in the Pathogenesis of Heart Disease and Coxsackieviral Myocarditis.” 2010. Masters Thesis, University of Toronto. Accessed March 07, 2021.
http://hdl.handle.net/1807/24657.
MLA Handbook (7th Edition):
Yuen, Stella Lai Yee. “The Role of the Coxsackie-adenovirus Receptor in the Pathogenesis of Heart Disease and Coxsackieviral Myocarditis.” 2010. Web. 07 Mar 2021.
Vancouver:
Yuen SLY. The Role of the Coxsackie-adenovirus Receptor in the Pathogenesis of Heart Disease and Coxsackieviral Myocarditis. [Internet] [Masters thesis]. University of Toronto; 2010. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/1807/24657.
Council of Science Editors:
Yuen SLY. The Role of the Coxsackie-adenovirus Receptor in the Pathogenesis of Heart Disease and Coxsackieviral Myocarditis. [Masters Thesis]. University of Toronto; 2010. Available from: http://hdl.handle.net/1807/24657
17.
van Oosten-Hawle, P.C.
Regulation of mitogen-activated protein kinase signaling by the molecular chaperones Hsp90 and Cdc37.
Degree: Faculty of Earth and Life Sciences, 2008, NARCIS
URL: https://research.vu.nl/en/publications/6a4f46c6-2c64-45d2-a134-75d291c639a3
;
urn:nbn:nl:ui:31-1871/15962
;
6a4f46c6-2c64-45d2-a134-75d291c639a3
;
1871/15962
;
urn:nbn:nl:ui:31-1871/15962
;
https://research.vu.nl/en/publications/6a4f46c6-2c64-45d2-a134-75d291c639a3
Subjects/Keywords: Cdc37; Hsp90; MAP kinase; molecular chaperones; signaling; yeast
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APA ·
Chicago ·
MLA ·
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APA (6th Edition):
van Oosten-Hawle, P. C. (2008). Regulation of mitogen-activated protein kinase signaling by the molecular chaperones Hsp90 and Cdc37. (Doctoral Dissertation). NARCIS. Retrieved from https://research.vu.nl/en/publications/6a4f46c6-2c64-45d2-a134-75d291c639a3 ; urn:nbn:nl:ui:31-1871/15962 ; 6a4f46c6-2c64-45d2-a134-75d291c639a3 ; 1871/15962 ; urn:nbn:nl:ui:31-1871/15962 ; https://research.vu.nl/en/publications/6a4f46c6-2c64-45d2-a134-75d291c639a3
Chicago Manual of Style (16th Edition):
van Oosten-Hawle, P C. “Regulation of mitogen-activated protein kinase signaling by the molecular chaperones Hsp90 and Cdc37.” 2008. Doctoral Dissertation, NARCIS. Accessed March 07, 2021.
https://research.vu.nl/en/publications/6a4f46c6-2c64-45d2-a134-75d291c639a3 ; urn:nbn:nl:ui:31-1871/15962 ; 6a4f46c6-2c64-45d2-a134-75d291c639a3 ; 1871/15962 ; urn:nbn:nl:ui:31-1871/15962 ; https://research.vu.nl/en/publications/6a4f46c6-2c64-45d2-a134-75d291c639a3.
MLA Handbook (7th Edition):
van Oosten-Hawle, P C. “Regulation of mitogen-activated protein kinase signaling by the molecular chaperones Hsp90 and Cdc37.” 2008. Web. 07 Mar 2021.
Vancouver:
van Oosten-Hawle PC. Regulation of mitogen-activated protein kinase signaling by the molecular chaperones Hsp90 and Cdc37. [Internet] [Doctoral dissertation]. NARCIS; 2008. [cited 2021 Mar 07].
Available from: https://research.vu.nl/en/publications/6a4f46c6-2c64-45d2-a134-75d291c639a3 ; urn:nbn:nl:ui:31-1871/15962 ; 6a4f46c6-2c64-45d2-a134-75d291c639a3 ; 1871/15962 ; urn:nbn:nl:ui:31-1871/15962 ; https://research.vu.nl/en/publications/6a4f46c6-2c64-45d2-a134-75d291c639a3.
Council of Science Editors:
van Oosten-Hawle PC. Regulation of mitogen-activated protein kinase signaling by the molecular chaperones Hsp90 and Cdc37. [Doctoral Dissertation]. NARCIS; 2008. Available from: https://research.vu.nl/en/publications/6a4f46c6-2c64-45d2-a134-75d291c639a3 ; urn:nbn:nl:ui:31-1871/15962 ; 6a4f46c6-2c64-45d2-a134-75d291c639a3 ; 1871/15962 ; urn:nbn:nl:ui:31-1871/15962 ; https://research.vu.nl/en/publications/6a4f46c6-2c64-45d2-a134-75d291c639a3
18.
Chung, Kwi-Mi.
Down-stream components of MAP kinase cascade in tobacco plants : タバコMAPKカスケードの下流因子; タバコ MAPK カスケード ノ カリュウ インシ.
Degree: Nara Institute of Science and Technology / 奈良先端科学技術大学院大学
URL: http://hdl.handle.net/10061/4068
Subjects/Keywords: MAP kinase
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APA (6th Edition):
Chung, K. (n.d.). Down-stream components of MAP kinase cascade in tobacco plants : タバコMAPKカスケードの下流因子; タバコ MAPK カスケード ノ カリュウ インシ. (Thesis). Nara Institute of Science and Technology / 奈良先端科学技術大学院大学. Retrieved from http://hdl.handle.net/10061/4068
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Chung, Kwi-Mi. “Down-stream components of MAP kinase cascade in tobacco plants : タバコMAPKカスケードの下流因子; タバコ MAPK カスケード ノ カリュウ インシ.” Thesis, Nara Institute of Science and Technology / 奈良先端科学技術大学院大学. Accessed March 07, 2021.
http://hdl.handle.net/10061/4068.
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Chung, Kwi-Mi. “Down-stream components of MAP kinase cascade in tobacco plants : タバコMAPKカスケードの下流因子; タバコ MAPK カスケード ノ カリュウ インシ.” Web. 07 Mar 2021.
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Vancouver:
Chung K. Down-stream components of MAP kinase cascade in tobacco plants : タバコMAPKカスケードの下流因子; タバコ MAPK カスケード ノ カリュウ インシ. [Internet] [Thesis]. Nara Institute of Science and Technology / 奈良先端科学技術大学院大学; [cited 2021 Mar 07].
Available from: http://hdl.handle.net/10061/4068.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.
Council of Science Editors:
Chung K. Down-stream components of MAP kinase cascade in tobacco plants : タバコMAPKカスケードの下流因子; タバコ MAPK カスケード ノ カリュウ インシ. [Thesis]. Nara Institute of Science and Technology / 奈良先端科学技術大学院大学; Available from: http://hdl.handle.net/10061/4068
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.
Université Laval
19.
Simard-Bisson, Carolyne.
Rôles de la "Dual leucine zipper-bearing Kinase" dans la
réorganisation des microtubules et la différenciation des
kératinocytes humains.
Degree: 2015, Université Laval
URL: http://hdl.handle.net/20.500.11794/28201
► La fonction barrière de la peau dépend en grande partie d’une différenciation appropriée des kératinocytes épidermiques. Au cours de ce processus, de nombreux changements ont…
(more)
▼ La fonction barrière de la peau dépend en grande
partie d’une différenciation appropriée des kératinocytes
épidermiques. Au cours de ce processus, de nombreux changements ont
lieu dans ces cellules tels que la diminution de la prolifération,
le remodelage du cytosquelette, des changements dans l’expression
génique, la dégradation du noyau et des organites de même que la
formation d’une structure bien particulière : l’enveloppe cornée.
Il est important que de tels évènements soient régulés de façon
adéquate puisqu’un débalancement au sein de ces derniers peut mener
à l’apparition de conditions pathologiques. La Dual Leucine
zipper-bearing
Kinase (DLK) est une Mitogen-Activated Protein
Kinase Kinase
Kinase dont l’expression est très forte au niveau de
la couche granuleuse, soit la dernière couche de cellules vivantes
avant la couche cornée de l’épiderme. Des études précédentes ont
révélé que la surexpression de la DLK dans des kératinocytes en
culture avait pour effet d’induire la différenciation terminale.
Toutefois, les mécanismes par lesquels la DLK régule ce processus
restent encore méconnus faisant en sorte que l’objectif général de
cette thèse consiste à mieux les définir. L’hypothèse à la base de
ces travaux est que la DLK est requise pour la différenciation des
kératinocytes et que celle-ci y participe en favorisant la
stabilisation des microtubules de même que l’expression ou
l’activité de facteurs de transcription impliqués dans ce
processus. Dans un premier temps, un modèle de peau reconstruite in
vitro dans lequel l’expression de la DLK a été réduite par
interférence à l’ARN a été développé. Il a été noté que la
diminution de la DLK avait pour effets d’affecter la distribution
de protéines de l’enveloppe cornée telles que la filaggrine et la
transglutaminase 1 de même que d’inhiber la formation des couches
granuleuse et cornée. Des analyses en immunofluorescence et en
microscopie électronique ont permis d’observer des défauts au
niveau des jonctions serrées et des desmosomes dans les peaux
sous-exprimant la DLK révélant un rôle de cette
kinase dans le bon
maintien de ces deux types de jonctions cellulaires. L’impact de la
DLK sur les microtubules a été étudié dans des kératinocytes en
culture transduits à l’aide de vecteurs adénoviraux menant à la
surexpression de la DLK de même que dans les peaux reconstruites
présentant une expression réduite de cette
kinase. Ces études ont
permis de conclure que la DLK était non seulement en mesure
d’induire la réorganisation et la stabilisation des microtubules en
périphérie cellulaire, mais que celle-ci était également requise à
la réalisation de ces processus. Afin de mieux décrire les
mécanismes par lesquels la DLK assure la réorganisation des
microtubules en périphérie cellulaire, les effets de la
surexpression ou de la sous-expression de la DLK sur les protéines
LIS1 et HSP27 (pour Heat shock protein 27 kDa), des régulateurs de
la distribution des microtubules, ont été étudiés. Ces analyses ont
permis de définir la DLK en tant qu’élément nécessaire à la bonne…
Advisors/Committee Members: Germain, Lucie, Blouin, Richard.
Subjects/Keywords: Microtubules; MAP kinase kinases; Kératinocytes
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APA ·
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MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Simard-Bisson, C. (2015). Rôles de la "Dual leucine zipper-bearing Kinase" dans la
réorganisation des microtubules et la différenciation des
kératinocytes humains. (Thesis). Université Laval. Retrieved from http://hdl.handle.net/20.500.11794/28201
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Simard-Bisson, Carolyne. “Rôles de la "Dual leucine zipper-bearing Kinase" dans la
réorganisation des microtubules et la différenciation des
kératinocytes humains.” 2015. Thesis, Université Laval. Accessed March 07, 2021.
http://hdl.handle.net/20.500.11794/28201.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Simard-Bisson, Carolyne. “Rôles de la "Dual leucine zipper-bearing Kinase" dans la
réorganisation des microtubules et la différenciation des
kératinocytes humains.” 2015. Web. 07 Mar 2021.
Vancouver:
Simard-Bisson C. Rôles de la "Dual leucine zipper-bearing Kinase" dans la
réorganisation des microtubules et la différenciation des
kératinocytes humains. [Internet] [Thesis]. Université Laval; 2015. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/20.500.11794/28201.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Simard-Bisson C. Rôles de la "Dual leucine zipper-bearing Kinase" dans la
réorganisation des microtubules et la différenciation des
kératinocytes humains. [Thesis]. Université Laval; 2015. Available from: http://hdl.handle.net/20.500.11794/28201
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
20.
Md. Tariqul, Islam.
Muscarinic cholinoceptor-mediated activation of JNK negatively regulates intestinal secretion in mice : ムスカリン性アセチルコリン受容体によるJNKの活性化はマウス腸管における分泌を負に制御する.
Degree: 博士（医学）, 2018, Asahikawa Medical University / 旭川医科大学
URL: http://amcor.asahikawa-med.ac.jp/modules/xoonips/detail.php?id=20180323_K524
► This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Regulation of intestinal secretion is important for body fluid homeostasis. We investigated the…
(more)
▼ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Regulation of intestinal secretion is important for body fluid homeostasis. We investigated the role of three MAP kinases (MAPKs) as negative regulators in muscarinic cholinoceptor (mAChR)-mediated intestinal secretion in mice. Electrophysiological analyses revealed that mAChR stimulation enhanced intestinal chloride secretion, which was further augmented by the inhibition of JNK but not by that of ERK or p38 with specific inhibitors SP600125, U0126 or SB203580, respectively. Immunoblot analyses in colonic mucosa showed that mAChR stimulation increased MAPKs phosphorylation that was suppressed by the specific inhibitor for each MAPK. This suggests that JNK is a major negative regulator in mAChR-induced intestinal secretion.
Subjects/Keywords: Intestinal secretion; MAP kinase; mAChR
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APA ·
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APA (6th Edition):
Md. Tariqul, I. (2018). Muscarinic cholinoceptor-mediated activation of JNK negatively regulates intestinal secretion in mice : ムスカリン性アセチルコリン受容体によるJNKの活性化はマウス腸管における分泌を負に制御する. (Thesis). Asahikawa Medical University / 旭川医科大学. Retrieved from http://amcor.asahikawa-med.ac.jp/modules/xoonips/detail.php?id=20180323_K524
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Md. Tariqul, Islam. “Muscarinic cholinoceptor-mediated activation of JNK negatively regulates intestinal secretion in mice : ムスカリン性アセチルコリン受容体によるJNKの活性化はマウス腸管における分泌を負に制御する.” 2018. Thesis, Asahikawa Medical University / 旭川医科大学. Accessed March 07, 2021.
http://amcor.asahikawa-med.ac.jp/modules/xoonips/detail.php?id=20180323_K524.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Md. Tariqul, Islam. “Muscarinic cholinoceptor-mediated activation of JNK negatively regulates intestinal secretion in mice : ムスカリン性アセチルコリン受容体によるJNKの活性化はマウス腸管における分泌を負に制御する.” 2018. Web. 07 Mar 2021.
Vancouver:
Md. Tariqul I. Muscarinic cholinoceptor-mediated activation of JNK negatively regulates intestinal secretion in mice : ムスカリン性アセチルコリン受容体によるJNKの活性化はマウス腸管における分泌を負に制御する. [Internet] [Thesis]. Asahikawa Medical University / 旭川医科大学; 2018. [cited 2021 Mar 07].
Available from: http://amcor.asahikawa-med.ac.jp/modules/xoonips/detail.php?id=20180323_K524.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Md. Tariqul I. Muscarinic cholinoceptor-mediated activation of JNK negatively regulates intestinal secretion in mice : ムスカリン性アセチルコリン受容体によるJNKの活性化はマウス腸管における分泌を負に制御する. [Thesis]. Asahikawa Medical University / 旭川医科大学; 2018. Available from: http://amcor.asahikawa-med.ac.jp/modules/xoonips/detail.php?id=20180323_K524
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
21.
Fukawa, Teruhisa; Kajiya, Hiroshi; Ozeki, Satoru; Ikebe, Tetsuro.
Reactive oxygen species stimulates epithelial mesenchymal transition in normal human epidermal keratinocytes via TGF-beta secretion. : Reactive oxygen species stimulates epithelial mesenchymal transition in normal human epidermal keratinocytes via TGF-beta secretion.
Degree: 博士（歯学）, 2014, Fukuoka Dental College / 福岡歯科大学
URL: http://id.nii.ac.jp/1167/00000021/
► Epithelial to mesenchymal transition (EMT) plays an important role in tumor progression, and is an early step in carcinogenesis. Although reactive oxygen species (ROS) are…
(more)
▼ Epithelial to mesenchymal transition (EMT) plays an important role in tumor progression, and is an early step in carcinogenesis. Although reactive oxygen species (ROS) are known to be implicated in EMT in many tumor cell types, its exact role in EMT initiation in normal human cells, especially epidermal keratinocytes (NHEKs), remains unknown. To clarify whether ROS induce EMT in NHEKs, and to establish how ROS regulate EMT, we examined the effect of hydrogen peroxide (H(2)O(2)) on the expression of molecules involved in EMT and cell morphology in NHEKs. H(2)O(2) altered the expression of EMT biomarkers, including downregulation of epithelial cadherin and upregulation of α-smooth muscle actin, through a transcriptional modulator, Snail1. H(2)O(2) also induced epithelial to fibroblast-like morphological changes, together with upregulation of EMT biomarkers, and promoted phosphorylation of ERK1/2 and JNK in a time-dependent manner. Interestingly, H(2)O(2) stimulated the expression and secretion of TGF-β1 in NHEKs. Exogenous TGF-β1 also induced the expression of EMT biomarkers. In contrast, neutralizing antibody anti-TGF-β1 antibody or inhibitor of TGF-β receptor type I suppressed the expression of EMT biomarkers. Our results suggest that ROS stimulated TGF-β1 secretion and MAPK activation, resulting in EMT initiation in NHEKs.
2013年度
Subjects/Keywords: Normal human epidermal keratinocyte; Epithelial to mesenchymal transition; Transforming growth factor-b1; Epithelial cadherin; a-smooth muscle actin; Actins; Base Sequence; Biological Markers; Cadherins; Cells, Cultured; DNA Primers; Epithelial-Mesenchymal Transition; Humans; Hydrogen Peroxide; Keratinocytes; MAP Kinase Signaling System; RNA, Messenger; Reactive Oxygen Species; Transcription Factors; Transforming Growth Factor beta; Up-Regulation
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APA ·
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MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Fukawa, Teruhisa; Kajiya, Hiroshi; Ozeki, Satoru; Ikebe, T. (2014). Reactive oxygen species stimulates epithelial mesenchymal transition in normal human epidermal keratinocytes via TGF-beta secretion. : Reactive oxygen species stimulates epithelial mesenchymal transition in normal human epidermal keratinocytes via TGF-beta secretion. (Thesis). Fukuoka Dental College / 福岡歯科大学. Retrieved from http://id.nii.ac.jp/1167/00000021/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Fukawa, Teruhisa; Kajiya, Hiroshi; Ozeki, Satoru; Ikebe, Tetsuro. “Reactive oxygen species stimulates epithelial mesenchymal transition in normal human epidermal keratinocytes via TGF-beta secretion. : Reactive oxygen species stimulates epithelial mesenchymal transition in normal human epidermal keratinocytes via TGF-beta secretion.” 2014. Thesis, Fukuoka Dental College / 福岡歯科大学. Accessed March 07, 2021.
http://id.nii.ac.jp/1167/00000021/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Fukawa, Teruhisa; Kajiya, Hiroshi; Ozeki, Satoru; Ikebe, Tetsuro. “Reactive oxygen species stimulates epithelial mesenchymal transition in normal human epidermal keratinocytes via TGF-beta secretion. : Reactive oxygen species stimulates epithelial mesenchymal transition in normal human epidermal keratinocytes via TGF-beta secretion.” 2014. Web. 07 Mar 2021.
Vancouver:
Fukawa, Teruhisa; Kajiya, Hiroshi; Ozeki, Satoru; Ikebe T. Reactive oxygen species stimulates epithelial mesenchymal transition in normal human epidermal keratinocytes via TGF-beta secretion. : Reactive oxygen species stimulates epithelial mesenchymal transition in normal human epidermal keratinocytes via TGF-beta secretion. [Internet] [Thesis]. Fukuoka Dental College / 福岡歯科大学; 2014. [cited 2021 Mar 07].
Available from: http://id.nii.ac.jp/1167/00000021/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Fukawa, Teruhisa; Kajiya, Hiroshi; Ozeki, Satoru; Ikebe T. Reactive oxygen species stimulates epithelial mesenchymal transition in normal human epidermal keratinocytes via TGF-beta secretion. : Reactive oxygen species stimulates epithelial mesenchymal transition in normal human epidermal keratinocytes via TGF-beta secretion. [Thesis]. Fukuoka Dental College / 福岡歯科大学; 2014. Available from: http://id.nii.ac.jp/1167/00000021/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
22.
山本, 梓司.
Protective and therapeutic role of 2-carba-cyclic phosphatidic acid in demyelinating disease. : 脱髄性疾患における環状ホスファチジン酸誘導体の脱髄抑制及び治療効果.
Degree: 博士(医学), 2018, Saitama Medical University / 埼玉医科大学
URL: http://id.nii.ac.jp/1386/00000615/
► Multiple sclerosis is a neuroinflammatory demyelinating and neurodegenerative disease of the central nervous system characterized by recurrent and progressive demyelination/remyelination cycles, neuroinflammation, oligodendrocyte loss, demyelination,…
(more)
▼ Multiple sclerosis is a neuroinflammatory demyelinating and neurodegenerative disease of the central nervous system characterized by recurrent and progressive demyelination/remyelination cycles, neuroinflammation, oligodendrocyte loss, demyelination, and axonal degeneration. Cyclic phosphatidic acid (cPA) is a natural phospholipid mediator with a unique cyclic phosphate ring structure at the sn-2 and sn-3 positions of the glycerol backbone. We reported earlier that cPA elicits a neurotrophin-like action and protects hippocampal neurons from ischemia-induced delayed neuronal death. We designed, chemically synthesized, and metabolically stabilized derivatives of cPA: 2-carba-cPA (2ccPA), a synthesized compound in which one of the phosphate oxygen molecules is replaced with a methylene group at the sn-2 position. In the present study, we investigated whether 2ccPA exerts protective effects in oligodendrocytes and suppresses pathology in the two most common mouse models of multiple sclerosis.
To evaluate whether 2ccPA has potential beneficial effects on the pathology of multiple sclerosis, we investigated the effects of 2ccPA on oligodendrocyte cell death in vitro and administrated 2ccPA to mouse models of experimental autoimmune encephalomyelitis (EAE) and cuprizone-induced demyelination.
We demonstrated that 2ccPA suppressed the CoCl
-induced increase in the Bax/Bcl-2 protein expression ratio and phosphorylation levels of p38MAPK and JNK protein. 2ccPA treatment reduced cuprizone-induced demyelination, microglial activation, NLRP3 inflammasome, and motor dysfunction. Furthermore, 2ccPA treatment reduced autoreactive T cells and macrophages, spinal cord injury, and pathological scores in EAE, the autoimmune multiple sclerosis mouse model.
We demonstrated that 2ccPA protected oligodendrocytes via suppression of the mitochondrial apoptosis pathway. Also, we found beneficial effects of 2ccPA in the multiperiod of cuprizone-induced demyelination and the pathology of EAE. These data indicate that 2ccPA may be a promising compound for the development of new drugs to treat demyelinating disease and ameliorate the symptoms of multiple sclerosis.
平成29年度
Subjects/Keywords: Animals; Anti-Inflammatory Agents; Apoptosis; Cell Differentiation; Cell Line, Transformed; Cuprizone; Demyelinating Diseases; Disease Models, Animal; Female; Gene Expression Regulation; Humans; MAP Kinase Signaling System; Male; Mice; Mice, Inbred C57BL; Monoamine Oxidase Inhibitors; Myelin Sheath; NLR Family, Pyrin Domain-Containing 3 Protein; Phosphatidic Acids; Proto-Oncogene Proteins c-bcl-2; p38 Mitogen-Activated Protein Kinases
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APA (6th Edition):
山本, . (2018). Protective and therapeutic role of 2-carba-cyclic phosphatidic acid in demyelinating disease. : 脱髄性疾患における環状ホスファチジン酸誘導体の脱髄抑制及び治療効果. (Thesis). Saitama Medical University / 埼玉医科大学. Retrieved from http://id.nii.ac.jp/1386/00000615/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
山本, 梓司. “Protective and therapeutic role of 2-carba-cyclic phosphatidic acid in demyelinating disease. : 脱髄性疾患における環状ホスファチジン酸誘導体の脱髄抑制及び治療効果.” 2018. Thesis, Saitama Medical University / 埼玉医科大学. Accessed March 07, 2021.
http://id.nii.ac.jp/1386/00000615/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
山本, 梓司. “Protective and therapeutic role of 2-carba-cyclic phosphatidic acid in demyelinating disease. : 脱髄性疾患における環状ホスファチジン酸誘導体の脱髄抑制及び治療効果.” 2018. Web. 07 Mar 2021.
Vancouver:
山本 . Protective and therapeutic role of 2-carba-cyclic phosphatidic acid in demyelinating disease. : 脱髄性疾患における環状ホスファチジン酸誘導体の脱髄抑制及び治療効果. [Internet] [Thesis]. Saitama Medical University / 埼玉医科大学; 2018. [cited 2021 Mar 07].
Available from: http://id.nii.ac.jp/1386/00000615/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
山本 . Protective and therapeutic role of 2-carba-cyclic phosphatidic acid in demyelinating disease. : 脱髄性疾患における環状ホスファチジン酸誘導体の脱髄抑制及び治療効果. [Thesis]. Saitama Medical University / 埼玉医科大学; 2018. Available from: http://id.nii.ac.jp/1386/00000615/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
23.
Takahashi, Satoe.
Plasma Membrane Localization of Signaling Proteins in Yeast: a Dissertation.
Degree: Interdisciplinary Graduate Program, Biochemistry and Molecular Pharmacology, 2008, U of Massachusetts : Med
URL: https://escholarship.umassmed.edu/gsbs_diss/364
► In response to external stimuli, many intracellular signaling proteins undergo dynamic changes in localization to the plasma membrane. Using the Saccharomyces cerevisiaemating pathway as…
(more)
▼ In response to external stimuli, many intracellular
signaling proteins undergo dynamic changes in localization to the plasma membrane. Using the
Saccharomyces cerevisiaemating pathway as a model, I investigated the molecular interactions that govern plasma membrane localization of
signaling proteins, and how the plasma membrane compartmentalization of a
signaling complex influences the overall
signaling behavior of the pathway.
Signaling proteins often consist of multiple interaction domains that collectively dictate their localization and function. Ste20 is a p21-activated
kinase (PAK) that functions downstream of the Rho-type GTPase Cdc42 to activate several mitogen-activated protein (
MAP)
kinase pathways in budding yeast, including the mating pathway. I identified a short domain in Ste20 that directly binds to membrane lipids via electrostatic interaction. A mutation in this domain abolishes both the localization and function of Ste20. Thus, the previously known Cdc42 binding is necessary but not sufficient; instead, direct membrane binding by Ste20 is also critical. By replacing this domain with heterologous membranebinding domains, I demonstrated that phospholipid specificity is not essential in vivo. Functionally important short membrane-binding domains were also found in the Cdc42 effectors Gic1 and Gic2, indicating that generic membrane binding can work in concert with the CRIB domain to regulate activation of Cdc42 targets. These results underscore the importance of cooperation between protein-protein and protein-membrane interaction in achieving proper localization of
signaling proteins at the cell cortex.
At the
system level,
MAP kinase cascades can be graded or switch-like. The budding yeast mating pathway exhibits a graded response to increasing levels of pheromone. Previously the scaffold protein Ste5 was hypothesized to contribute to this graded response. To test this idea, I activated the pathway in a variety of ways and measured the response at the single cell level. I found that the graded response is not perturbed by the deletion of negative regulators of the pathway whereas the response became switch-like when the pathway was activated by a crosstalk stimulus that bypasses the upstream components. Interestingly, activation of the pathway in the cytoplasm using the graded expression of MAPKKK resulted in an ultrasensitive response. In contrast, activation of the pathway at the plasma membrane using the graded expression of membranetargeted active pathway components remained graded. In these settings, the scaffold protein Ste5 increased ultrasensitivity when limited to the cytosol; however, if Ste5 was allowed to function at the plasma membrane,
signaling was graded. The results suggest that, in the mating pathway, the inherently ultrasensitive MAPK cascade is converted to a graded
system by the scaffoldmediated assembly of
signaling complexes at the plasma membrane. Therefore, the plasma membrane localization of Ste5 helps shape the input-output properties of the mating…
Advisors/Committee Members: Peter M. Pryciak, Ph.D..
Subjects/Keywords: Cell Membrane; Saccharomyces cerevisiae; cdc42 GTP-Binding Protein; MAP Kinase Signaling System; Saccharomyces cerevisiae Proteins; Signal Transduction; Amino Acids, Peptides, and Proteins; Cells; Enzymes and Coenzymes; Fungi
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APA ·
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APA (6th Edition):
Takahashi, S. (2008). Plasma Membrane Localization of Signaling Proteins in Yeast: a Dissertation. (Doctoral Dissertation). U of Massachusetts : Med. Retrieved from https://escholarship.umassmed.edu/gsbs_diss/364
Chicago Manual of Style (16th Edition):
Takahashi, Satoe. “Plasma Membrane Localization of Signaling Proteins in Yeast: a Dissertation.” 2008. Doctoral Dissertation, U of Massachusetts : Med. Accessed March 07, 2021.
https://escholarship.umassmed.edu/gsbs_diss/364.
MLA Handbook (7th Edition):
Takahashi, Satoe. “Plasma Membrane Localization of Signaling Proteins in Yeast: a Dissertation.” 2008. Web. 07 Mar 2021.
Vancouver:
Takahashi S. Plasma Membrane Localization of Signaling Proteins in Yeast: a Dissertation. [Internet] [Doctoral dissertation]. U of Massachusetts : Med; 2008. [cited 2021 Mar 07].
Available from: https://escholarship.umassmed.edu/gsbs_diss/364.
Council of Science Editors:
Takahashi S. Plasma Membrane Localization of Signaling Proteins in Yeast: a Dissertation. [Doctoral Dissertation]. U of Massachusetts : Med; 2008. Available from: https://escholarship.umassmed.edu/gsbs_diss/364
24.
Cao, Cong.
The role of inhibitory heterotrimeric G proteins in Receptor
Tyrosine Kinase function and identification of defective TrkB
signaling in Angelman Syndrome.
Degree: PhD, Pathobiology, 2011, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:11272/
► The Epidermal growth factor (EGF) receptor (EGFR), tropomyosin-receptor kinase (Trk) and other receptor tyrosine kinase (RTK) family members play pivotal roles in regulating the normal…
(more)
▼ The Epidermal growth factor (EGF) receptor (EGFR),
tropomyosin-receptor
kinase (Trk) and other receptor tyrosine
kinase (RTK) family members play pivotal roles in regulating the
normal biological process and malignant transformation. They
activate downstream transduction signal transduction cascades, that
include the phosphoinositide 3-
kinase (PI3K) /AKT/ mammalian target
of rapamycin complex 1 (mTORC1) and mitogen-activated protein
kinase (MAPK) pathways, which are vital for cell proliferation,
growth, migration and survival. However, it is still not entirely
understood how the RTK transduces signals to PI3K/AKT/ mTORC1 and
MAPK. The first part of this thesis focuses on the role of
heterotrimeric G protein alpha subunits, Gai1 and Gai3, in this
process. We identify an association of Gai proteins with the RTK
and the adaptor protein Gab1 (Grb2 associated bind 1). This
interaction is required for subsequent Gab1 phosphorylation, and
downstream activation of the AKT-mTOR and the MAPK pathways in
response to RTK ligands, including EGF and brain-derived
neurotrophic factor (BDNF). This study demonstrates a novel role
between Gai proteins, traditionally known as components in
G-protein coupled receptor (GPCR)
signaling, and RTK
signaling.
Angelman Syndrome (AS) is a neurological disorder caused by a loss
of maternal expression of the ubiquitin E3 ligase gene UBE3A.
Common symptoms of AS include developmental delay, mental
retardation, excessive inappropriate laughter, movement ataxia,
seizures, and lack of speech. The precise molecular mechanisms
which cause the symptoms of Angelman Syndrome, however, are still
not completely understood. We discovered that BDNF/TrkB
signaling
is deficient in Angelman Syndrome (AS) mice, providing a possible
explanation for LTP (long-term potentiation) loss and other
symptoms associated with Angelman Syndrome. CN 2097, a newly
synthesized cyclic peptide designed to target the PDZ domains of
the PSD-95, rescued BDNF
signaling and LTP in AS mice. PSD-95 forms
a complex with TrkB after BDNF treatment and CN 2097 increased this
association to enhance PI3K/AKT and CaMKII
signaling. This study
suggests that CN 2097 may represent a new therapeutic option for
treating this disease.
Advisors/Committee Members: Marshall, John (Director), Bowen, Wayne (Reader), Green, William (Reader), Biron, Christine (Reader), Reichner, Jonathan (Reader).
Subjects/Keywords: receptor tyrosine kinase signaling
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APA ·
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Export
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Manager
APA (6th Edition):
Cao, C. (2011). The role of inhibitory heterotrimeric G proteins in Receptor
Tyrosine Kinase function and identification of defective TrkB
signaling in Angelman Syndrome. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:11272/
Chicago Manual of Style (16th Edition):
Cao, Cong. “The role of inhibitory heterotrimeric G proteins in Receptor
Tyrosine Kinase function and identification of defective TrkB
signaling in Angelman Syndrome.” 2011. Doctoral Dissertation, Brown University. Accessed March 07, 2021.
https://repository.library.brown.edu/studio/item/bdr:11272/.
MLA Handbook (7th Edition):
Cao, Cong. “The role of inhibitory heterotrimeric G proteins in Receptor
Tyrosine Kinase function and identification of defective TrkB
signaling in Angelman Syndrome.” 2011. Web. 07 Mar 2021.
Vancouver:
Cao C. The role of inhibitory heterotrimeric G proteins in Receptor
Tyrosine Kinase function and identification of defective TrkB
signaling in Angelman Syndrome. [Internet] [Doctoral dissertation]. Brown University; 2011. [cited 2021 Mar 07].
Available from: https://repository.library.brown.edu/studio/item/bdr:11272/.
Council of Science Editors:
Cao C. The role of inhibitory heterotrimeric G proteins in Receptor
Tyrosine Kinase function and identification of defective TrkB
signaling in Angelman Syndrome. [Doctoral Dissertation]. Brown University; 2011. Available from: https://repository.library.brown.edu/studio/item/bdr:11272/
University of Sydney
25.
Domanova, Westa.
Unraveling the regulation of phosphorylation in insulin singaling from temporal large-scale phosphoproteomics
.
Degree: 2017, University of Sydney
URL: http://hdl.handle.net/2123/16704
► Homeostasis is essential for normal function of the mammalian body. On a cellular scale biological processes are tightly controlled by dynamic intracellular signalling mechanisms. Cells…
(more)
▼ Homeostasis is essential for normal function of the mammalian body. On a cellular scale biological processes are tightly controlled by dynamic intracellular signalling mechanisms. Cells use intricate signalling networks to respond to environmental cues and appropriately regulate functions such as differentiation, metabolism and proliferation. Deregulated signalling can result in complex diseases such as cancer, neurodegenerative diseases and cancer. Signals inside cells are transmitted via protein phosphorylation. Protein phosphorylation is a reversible chemical modification where a phosphate group is attached to a protein by enzymes (kinases). Phosphatases are responsible for the reverse reaction. Protein phosphorylation occurs on rapid time-scales (milliseconds to seconds), making it an ideal carrier of these signals. Advances in mass spectrometry-based proteomics have led to the identification of many tens of thousands of phosphorylation sites. The improvement of the technique has also recently allowed us to measure phosphorylation over time on a large scale. The analysis on these temporal datasets did not differ from the analysis applied to static datasets. However, temporal data offers more possibilities for knowledge discovery and more intricate analysis methods can be applied to interrogate the time course data. This work focuses on the development and application of analysis techniques for large-scale temporal phosphoproteomics data. Using these techniques it is possible to identify kinases that are involved in a signalling process, it is possible to predict which phosphorylation sites are important and it is possible to find gaps in the knowledge of a signalling network. The results from this work will direct further experimental studies. Taken together, the analysis techniques applied in this work can help our understanding of intracellular signalling and this in turn can facilitate drug discovery
Subjects/Keywords: phosphoproteomics;
kinase;
cell signaling
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Domanova, W. (2017). Unraveling the regulation of phosphorylation in insulin singaling from temporal large-scale phosphoproteomics
. (Thesis). University of Sydney. Retrieved from http://hdl.handle.net/2123/16704
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Domanova, Westa. “Unraveling the regulation of phosphorylation in insulin singaling from temporal large-scale phosphoproteomics
.” 2017. Thesis, University of Sydney. Accessed March 07, 2021.
http://hdl.handle.net/2123/16704.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Domanova, Westa. “Unraveling the regulation of phosphorylation in insulin singaling from temporal large-scale phosphoproteomics
.” 2017. Web. 07 Mar 2021.
Vancouver:
Domanova W. Unraveling the regulation of phosphorylation in insulin singaling from temporal large-scale phosphoproteomics
. [Internet] [Thesis]. University of Sydney; 2017. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/2123/16704.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Domanova W. Unraveling the regulation of phosphorylation in insulin singaling from temporal large-scale phosphoproteomics
. [Thesis]. University of Sydney; 2017. Available from: http://hdl.handle.net/2123/16704
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
26.
Brancho, Deborah Marie.
Regulation and Function of Stress-Activated Protein Kinase Signal Transduction Pathways: A Dissertation.
Degree: Interdisciplinary Graduate Program, Program in Molecular Medicine, 2005, U of Massachusetts : Med
URL: https://escholarship.umassmed.edu/gsbs_diss/101
► The c-Jun NH2-terminal kinase (JNK) group and the p38 group of mitogen-activated protein kinases (MAPK) are stress-activated protein kinases that regulate cell proliferation, differentiation,…
(more)
▼ The c-Jun NH
2-terminal
kinase (JNK) group and the p38 group of mitogen-activated protein kinases (MAPK) are stress-activated protein kinases that regulate cell proliferation, differentiation, development, and apoptosis. These protein kinases are involved in a signal transduction cascade that includes a
MAP kinase (MAPK), a
MAP kinase kinase (MAP2K), and a
MAP kinase kinase
kinase (MAP3K). MAPK are phosphorylated and activated by the MAP2K, which are phosphorylated and activated by various MAP3K.
The work presented in this dissertation focuses on understanding the regulation and function of the JNK and p38 MAPK pathways. Two different strategies were utilized. First, I used molecular and biochemical techniques to examine how MAP2K and MAP3K mediate
signaling specificity and to define their role in the MAPK pathway. Second, I used gene targeted disruption studies to determine the
in vivo role ofMAP2K and MAP3K in MAPK activation. I specifically used these approaches to examine: (1) docking interactions between p38 MAPK and MAP2K [MKK3 and MKK6 (Chapter II)]; (2) the differential activation of p38 MAPK by MAP2K [MKK3, MKK4, and MKK6 (Chapter III)]; and (3) the selective involvement of the mixed lineage
kinase (MLK) group of MAP3K in JNK and p38 MAPK activation (Chapter IV and Appendix). In addition, I analyzed the role of the MKK3 and MKK6 MAP2K in cell proliferation and the role of the MLK MAP3K in adipocyte differentiation (Chapter III and Chapter IV). Together, these data provide insight into the regulation and function of the stress-activated MAPK signal transduction pathways.
Advisors/Committee Members: Roger J. Davis, Ph.D..
Subjects/Keywords: p38 Mitogen-Activated Protein Kinases; JNK Mitogen-Activated Protein Kinases; Mitogen-Activated Protein Kinase Kinases; MAP Kinase Signaling System; Cell Differentiation; Adipocytes; Amino Acids, Peptides, and Proteins; Cells; Enzymes and Coenzymes
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APA ·
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MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Brancho, D. M. (2005). Regulation and Function of Stress-Activated Protein Kinase Signal Transduction Pathways: A Dissertation. (Doctoral Dissertation). U of Massachusetts : Med. Retrieved from https://escholarship.umassmed.edu/gsbs_diss/101
Chicago Manual of Style (16th Edition):
Brancho, Deborah Marie. “Regulation and Function of Stress-Activated Protein Kinase Signal Transduction Pathways: A Dissertation.” 2005. Doctoral Dissertation, U of Massachusetts : Med. Accessed March 07, 2021.
https://escholarship.umassmed.edu/gsbs_diss/101.
MLA Handbook (7th Edition):
Brancho, Deborah Marie. “Regulation and Function of Stress-Activated Protein Kinase Signal Transduction Pathways: A Dissertation.” 2005. Web. 07 Mar 2021.
Vancouver:
Brancho DM. Regulation and Function of Stress-Activated Protein Kinase Signal Transduction Pathways: A Dissertation. [Internet] [Doctoral dissertation]. U of Massachusetts : Med; 2005. [cited 2021 Mar 07].
Available from: https://escholarship.umassmed.edu/gsbs_diss/101.
Council of Science Editors:
Brancho DM. Regulation and Function of Stress-Activated Protein Kinase Signal Transduction Pathways: A Dissertation. [Doctoral Dissertation]. U of Massachusetts : Med; 2005. Available from: https://escholarship.umassmed.edu/gsbs_diss/101
27.
Wysk, Mark Allen.
The Role of MKK3 in Mediating Signals to the p38 MAP Kinase Pathway: A Dissertation.
Degree: Biochemistry and Molecular Pharmacology, Program in Molecular Medicine, 2000, U of Massachusetts : Med
URL: https://escholarship.umassmed.edu/gsbs_diss/184
► p38 mitogen-activated protein (MAP) kinases represent a subgroup of MAP kinases that respond to environmental stress and inflammatory cytokines. p38 MAPK is activated by…
(more)
▼ p38 mitogen-activated protein (
MAP) kinases represent a subgroup of
MAP kinases that respond to environmental stress and inflammatory cytokines. p38 MAPK is activated by two upstream kinases, MKK3 and MKK6, by dual phosphorylation on threonine and tyrosine in conserved
kinase subdomain VII. Until recently the relative roles of MKK3 and MKK6 have remained unclear. I have undertaken two strategies in an effort to understand the importance of MKK3 as a p38 MAPK activator. First, I cloned and characterized the murine
mkk3 gene and determined the structure of the 5'-terminus. Comparison of the murine and human
mkk3 genes revealed that the mouse gene encodes a single MKK3 isoform, MKK3b, and the human gene encodes two isoforms, MKK3a and MKK3b. Comparison of the mouse and human
mkk3 genes suggests that expression of MKK3a and MKK3b is regulated from different promotors. Analysis of the mkk3 promoter demonstrates that muscle specific expression of murine MKK3b is controlled, in part, by the transcription factors MEF2 and MyoD. Second, I have utilized a gene targeting strategy to disrupt the murine
mkk3 gene and to examine the effect on p38 MAPK
signaling. I found that there is a p38-specific
signaling defect in MKK3 deficient primary mouse embryo fibroblasts (MEF) which correlates with deficits in interleukin (IL)-1 and IL-6 production in response to tumor necrosis factor-α (TNFα) stimulation. In addition there is a defect in TNFα mediated expression of TNFα and macrophage inflammatory proteins (MIP) 1α, MIP1β and MIP2. p38 MAPK-specific
signaling defects were also observed in lipopolysaccharide (LPS) stimulated
mkk3 (-/-) macrophages. Additionally,
mkk3 (-/-) macrophages exhibit defects in LPS and CD40-ligand (CD40L) stimulated IL-12 biosynthesis. Similar data were obtained from CD40L-stimulated
mkk3 (-/-) dendritic cells. I also observe that interferon (Ifn)-γ production is diminished during T-helper-1 (T
H1) differentiation of CD4
+ T-cells derived from
mkk3 (-/-) mice. Taken together these data demonstrate a crucial role for p38 MAPK activation by MKK3 in response to the inflammatory cytokine, TNFα and during a T
H1 inflammatory response.
Advisors/Committee Members: Roger J. Davis, Ph.D..
Subjects/Keywords: MAP Kinase Signaling System; Mitogen-Activated Protein Kinase Kinases; Mitogen-Activated Protein Kinases; Signal Transduction; Amino Acids, Peptides, and Proteins; Cells; Chemical Actions and Uses; Enzymes and Coenzymes
Record Details
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Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wysk, M. A. (2000). The Role of MKK3 in Mediating Signals to the p38 MAP Kinase Pathway: A Dissertation. (Doctoral Dissertation). U of Massachusetts : Med. Retrieved from https://escholarship.umassmed.edu/gsbs_diss/184
Chicago Manual of Style (16th Edition):
Wysk, Mark Allen. “The Role of MKK3 in Mediating Signals to the p38 MAP Kinase Pathway: A Dissertation.” 2000. Doctoral Dissertation, U of Massachusetts : Med. Accessed March 07, 2021.
https://escholarship.umassmed.edu/gsbs_diss/184.
MLA Handbook (7th Edition):
Wysk, Mark Allen. “The Role of MKK3 in Mediating Signals to the p38 MAP Kinase Pathway: A Dissertation.” 2000. Web. 07 Mar 2021.
Vancouver:
Wysk MA. The Role of MKK3 in Mediating Signals to the p38 MAP Kinase Pathway: A Dissertation. [Internet] [Doctoral dissertation]. U of Massachusetts : Med; 2000. [cited 2021 Mar 07].
Available from: https://escholarship.umassmed.edu/gsbs_diss/184.
Council of Science Editors:
Wysk MA. The Role of MKK3 in Mediating Signals to the p38 MAP Kinase Pathway: A Dissertation. [Doctoral Dissertation]. U of Massachusetts : Med; 2000. Available from: https://escholarship.umassmed.edu/gsbs_diss/184
Université de Grenoble
28.
Kragelj, Jaka.
Structure and dynamics of intrinsically disordered regions of MAPK signalling proteins : Structure et dynamique des régions intrinsèquement désordonnées des MAPK.
Degree: Docteur es, Biologie structurale et nanobiologie, 2014, Université de Grenoble
URL: http://www.theses.fr/2014GRENV060
► Les voies de transduction du signal cellulaire permettent aux cellules de répondre aux signaux de l'environnement et de les traiter. Les voies de transduction de…
(more)
▼ Les voies de transduction du signal cellulaire permettent aux cellules de répondre aux signaux de l'environnement et de les traiter. Les voies de transduction de kinases MAP (MAPK) sont bien conservées dans toutes les cellules eucaryotes et sont impliquées dans la régulation de nombreux processus cellulaires importants. Les régions intrinsèquement désordonnées (RID), présentes dans de nombreuses MAPK, n'étaient pas encore structurellement caractérisées. Les RID de MAPK sont particulièrement importantes car elles contiennent des motifs de liaison qui contrôlent les interactions entre les protéines MAPK elles-mêmes et aussi entre les protéines MAPK et d'autres protéines contenant les mêmes motifs. La résonance magnétique nucléaire (RMN) en combinaison avec d'autres techniques biophysiques a été utilisée pour étudier les RID de kinase des voies de transduction du signal MAPK. La spectroscopie RMN est bien adaptée pour l'étude des protéines intrinsèquement désordonnées à l'échelle atomique. Les déplacements chimiques et couplages dipolaires résiduels peuvent être utilisés conjointement avec des méthodes de sélection d'ensemble pour étudier la structure résiduelle dans les RID. La relaxation de spin nucléaire nous renseigne sur les mouvements rapides. Des titrations par RMN et des techniques de spectroscopie d'échange peuvent être utilisées pour surveiller la cinétique d'interactions protéine-protéine. Cette étude contribuera à la compréhension du rôle des RID dans les voies de transduction du signal cellulaire.
Protein signal transduction pathways allow cells respond to and process signals from the environment. A group of such pathways, called mitogen-activated protein kinase (MAPK) signal transduction pathways, is well conserved in all eukaryotic cells and is involved in regulating many important cell processes. Long intrinsically disordered region (IDRs), present in many MAPKs, have remained structurally uncharacterised. The IDRs of MAPKs are especially important as they contain docking-site motifs which control the interactions between MAPK proteins themselves and also between MAPKs and other interacting proteins containing the same motifs. Nuclear magnetic resonance (NMR) spectroscopy in combination with other biophysical techniques was used to study IDRs of MAPKs. NMR spectroscopy is well suited for studying intrinsically disordered proteins (IDPs) at atomic-level resolution. NMR observables, such as for example chemical shifts and residual dipolar couplings, can be used together with ensemble selection methods to study residual structure in IDRs. Nuclear spin relaxation informs us about fast pico-nanosecond motions. NMR titrations and exchange spectroscopy techniques can be used to monitor kinetics of protein-protein interactions. The mechanistic insight into function of IDRs and motifs will contribute to understanding of how signal transduction pathways work.
Advisors/Committee Members: Jensen, Malene (thesis director), Blackledge, Martin (thesis director).
Subjects/Keywords: RMN; Couplages dipolaires résiduels; Structure des protéines; Kinases kinases activees par un mitogene; Signalisation des MAP Kinases; Proteines intrinsèquement; RMN; Couplages dipolaires residuels; Protein structure; Mitogen-activated protein kinase kinases; MAP Kinase Signaling; Intrinsically disordered proteins; 570
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APA (6th Edition):
Kragelj, J. (2014). Structure and dynamics of intrinsically disordered regions of MAPK signalling proteins : Structure et dynamique des régions intrinsèquement désordonnées des MAPK. (Doctoral Dissertation). Université de Grenoble. Retrieved from http://www.theses.fr/2014GRENV060
Chicago Manual of Style (16th Edition):
Kragelj, Jaka. “Structure and dynamics of intrinsically disordered regions of MAPK signalling proteins : Structure et dynamique des régions intrinsèquement désordonnées des MAPK.” 2014. Doctoral Dissertation, Université de Grenoble. Accessed March 07, 2021.
http://www.theses.fr/2014GRENV060.
MLA Handbook (7th Edition):
Kragelj, Jaka. “Structure and dynamics of intrinsically disordered regions of MAPK signalling proteins : Structure et dynamique des régions intrinsèquement désordonnées des MAPK.” 2014. Web. 07 Mar 2021.
Vancouver:
Kragelj J. Structure and dynamics of intrinsically disordered regions of MAPK signalling proteins : Structure et dynamique des régions intrinsèquement désordonnées des MAPK. [Internet] [Doctoral dissertation]. Université de Grenoble; 2014. [cited 2021 Mar 07].
Available from: http://www.theses.fr/2014GRENV060.
Council of Science Editors:
Kragelj J. Structure and dynamics of intrinsically disordered regions of MAPK signalling proteins : Structure et dynamique des régions intrinsèquement désordonnées des MAPK. [Doctoral Dissertation]. Université de Grenoble; 2014. Available from: http://www.theses.fr/2014GRENV060
Indian Institute of Science
29.
Agrawal, Ruchi.
Systemic Profiling of Two Component Signaling Networks in Mycobacterium Tuberculosis.
Degree: PhD, Faculty of Science, 2018, Indian Institute of Science
URL: http://etd.iisc.ac.in/handle/2005/3591
► Mycobacterium tuberculosis, the causative organism of the disease tuberculosis (TB) in humans, leads to nearly two million deaths each year. This versatile pathogen can exist…
(more)
▼ Mycobacterium tuberculosis, the causative organism of the disease tuberculosis (TB) in humans, leads to nearly two million deaths each year. This versatile pathogen can exist in highly distinct physiological states such as asymptomatic latent TB infection where bacilli lie dormant or as active TB disease in which the bacilli replicate in macrophages. The pathogenic lifestyle requires the tubercle bacillus to sense and respond to multiple environmental cues to ensure its survival. Such stimuli include hypoxia, nutrient limitation, presence of reactive oxygen and reactive nitrogen intermediates, pH alterations, and cell wall/ membrane stress. Two component systems (TCSs) form the primary apparatus for sensing and responding to environmental cues in bacteria. A prototypical TCS is composed of a sensory protein called sensor
kinase (SK) and a response generating protein called response regulator (RR).
M. tuberculosis encodes 11 genetically paired TCSs, 2 orphan sensor kinases and six orphan response regulator proteins. Studies of the TB bacilli using transcriptional profiling and gene knockouts have revealed that TCSs play an important role in facilitating successful adaptation to diverse environmental conditions encountered within the host. The mtrAB and prrAB genes encoding corresponding TCSs have been shown to be essential for survival, mprAB for persistence and devRS for hypoxic adaptation. Further, inactivation of the TCSs regX3-senX3, tcrXY, trcRS, phoPR or kdpDE was shown to affect the growth and/or virulence of M. tuberculosis in animal infection models.
The SK and RR proteins of TCSs are modular and contain variable input and output domains coupled to conserved ‘transmitter’ and ‘receiver’ domains. Despite the modular nature and extensive homology of SK and RR proteins across TCSs, which may allow non-cognate interactions, it is believed that crosstalk across different TCSs is not favored and that individual pathways are generally well insulated. The existing profiling studies have been performed on the TCSs of bacterial species containing a relatively large number of TCSs. In those studies, specificity and insulation have been the norm and thus become the prevalent paradigm of TCS
signaling. In vitro genome wide phosphotransfer profiling has revealed only a few cross- communication nodes in the TCSs of Escherichia coli (~3%), while none in Caulobacter crescentus (in 352 interactions tested, in short time duration) and Myxococcus xanthus (in 250 interactions tested).
Yet, many instances of cross talk have been reported in literature. For example, E. coli TCSs PmrAB and EnvZ-OmpR show cross-communication with QseBC and ArcBA, and many more. In M. tuberculosis, indirect evidence of the existence of such cross regulation has originated from studies where mutations in phoPR have been shown to affect the expression of the TCS devRS and its regulon. It is thus interesting to examine the extent of crosstalk in the TCSs of M. tuberculosis, which has an exceptionally small number of TCS proteins compared to E. coli. …
Advisors/Committee Members: Saini, Deepak K (advisor).
Subjects/Keywords: Mycobacterium tuberculosis; Two Component Signaling Networks; Bacterial Two Component Signaling Systems; Sensor Histidine Kinase; Response Regulator; Mycobacterium tuberculosis Two Component Systems; Two Component System Proteins; Two Component Signal Transduction; NarS Sensor Kinase; Two-Component Signaling Systems; Two-Component Systems; Molecular Biology
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APA (6th Edition):
Agrawal, R. (2018). Systemic Profiling of Two Component Signaling Networks in Mycobacterium Tuberculosis. (Doctoral Dissertation). Indian Institute of Science. Retrieved from http://etd.iisc.ac.in/handle/2005/3591
Chicago Manual of Style (16th Edition):
Agrawal, Ruchi. “Systemic Profiling of Two Component Signaling Networks in Mycobacterium Tuberculosis.” 2018. Doctoral Dissertation, Indian Institute of Science. Accessed March 07, 2021.
http://etd.iisc.ac.in/handle/2005/3591.
MLA Handbook (7th Edition):
Agrawal, Ruchi. “Systemic Profiling of Two Component Signaling Networks in Mycobacterium Tuberculosis.” 2018. Web. 07 Mar 2021.
Vancouver:
Agrawal R. Systemic Profiling of Two Component Signaling Networks in Mycobacterium Tuberculosis. [Internet] [Doctoral dissertation]. Indian Institute of Science; 2018. [cited 2021 Mar 07].
Available from: http://etd.iisc.ac.in/handle/2005/3591.
Council of Science Editors:
Agrawal R. Systemic Profiling of Two Component Signaling Networks in Mycobacterium Tuberculosis. [Doctoral Dissertation]. Indian Institute of Science; 2018. Available from: http://etd.iisc.ac.in/handle/2005/3591
30.
Strickfaden, Shelly Catherine.
Regulation of Cell Polarization and Map Kinase Signaling in the Saccharomyces Cerevisiae Pheromone Response Pathway: a Dissertation.
Degree: Interdisciplinary Graduate Program, Biochemistry and Molecular Pharmacology, 2007, U of Massachusetts : Med
URL: https://escholarship.umassmed.edu/gsbs_diss/321
► Exposure to external stimuli promotes a variety of cellular responses including changes in morphology, gene expression and cell division status. These responses are promoted…
(more)
▼ Exposure to external stimuli promotes a variety of cellular responses including changes in morphology, gene expression and cell division status. These responses are promoted by
signaling pathways composed of modules that are conserved from lower to higher eukaryotes. In
Saccharomyces cerevisiae response to the external stimuli provided by mating pheromone is governed by the pheromone response pathway. This pathway is composed of a G protein coupled receptor/heterotrimeric G protein (Gαβγ) module and a
MAP kinase cascade. Activation of this pathway allows the heterotrimeric G protein βγ dimer (Gβγ) to recruit polarity proteins to promote changes in cell morphology and to activate
signaling through the
MAP kinase cascade. Here we investigate the regulation of these pheromone-induced responses.
We first examine how an asymmetric polarization response is generated. Normally, a gradient of pheromone serves as a spatial cue for formation of a polarized mating projection, but cells can still polarize when pheromone is present uniformly. Here we show that an intact receptor/Gαβγ module is required for polarization in response to both a gradient and uniform concentration of pheromone. Further investigation into regulation of Gβγ by Gα revealed that the two interaction interfaces between Gα and Gβ have qualitatively different roles. Our results suggest that one interface controls
signaling whereas the other governs coupling to the receptor. Overall our results indicate that communication between the receptor and Gαβγ is required for proper polarization.
We then examine how G1 CDKs regulate
MAP kinase signaling. Response to pheromone is restricted to the G1 stage of the cell cycle. Once cells commit to a round of division they become refractory to mating pheromone until that round of division is complete. One contributor to this specificity involves inhibition of
signaling through the
MAP kinase cascade by G1 CDKs, but it was not known how this occurs. Here, we show that the
MAP kinase cascade scaffold Ste5 is the target of this inhibition. Cln/CDKs inhibit
signaling by phosphorylating sites surrounding a small membrane-binding domain in Ste5, thereby disrupting the membrane localization of Ste5. Furthermore, we found that disrupting this regulation allows cells to arrest at an aberrant non-G1 position. Our findings define a mechanism and a physiological benefit for restricting pheromone-induced
signaling to G1.
This thesis describes findings related to generation of an asymmetric polarization response, heterotrimeric G protein function, and coordination of differentiation
signaling with cell division status. Lessons learned here might be applicable to the regulation of polarization and differentiation responses in other systems as the
signaling modules are conserved.
Advisors/Committee Members: Peter Pryciak, Ph.D..
Subjects/Keywords: Adaptor Proteins; Signal Transducing; G1 Phase; MAP Kinase Signaling System; Mitogen-Activated Protein Kinases; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Amino Acids, Peptides, and Proteins; Enzymes and Coenzymes; Fungi
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APA ·
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APA (6th Edition):
Strickfaden, S. C. (2007). Regulation of Cell Polarization and Map Kinase Signaling in the Saccharomyces Cerevisiae Pheromone Response Pathway: a Dissertation. (Doctoral Dissertation). U of Massachusetts : Med. Retrieved from https://escholarship.umassmed.edu/gsbs_diss/321
Chicago Manual of Style (16th Edition):
Strickfaden, Shelly Catherine. “Regulation of Cell Polarization and Map Kinase Signaling in the Saccharomyces Cerevisiae Pheromone Response Pathway: a Dissertation.” 2007. Doctoral Dissertation, U of Massachusetts : Med. Accessed March 07, 2021.
https://escholarship.umassmed.edu/gsbs_diss/321.
MLA Handbook (7th Edition):
Strickfaden, Shelly Catherine. “Regulation of Cell Polarization and Map Kinase Signaling in the Saccharomyces Cerevisiae Pheromone Response Pathway: a Dissertation.” 2007. Web. 07 Mar 2021.
Vancouver:
Strickfaden SC. Regulation of Cell Polarization and Map Kinase Signaling in the Saccharomyces Cerevisiae Pheromone Response Pathway: a Dissertation. [Internet] [Doctoral dissertation]. U of Massachusetts : Med; 2007. [cited 2021 Mar 07].
Available from: https://escholarship.umassmed.edu/gsbs_diss/321.
Council of Science Editors:
Strickfaden SC. Regulation of Cell Polarization and Map Kinase Signaling in the Saccharomyces Cerevisiae Pheromone Response Pathway: a Dissertation. [Doctoral Dissertation]. U of Massachusetts : Med; 2007. Available from: https://escholarship.umassmed.edu/gsbs_diss/321
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Open Access Theses and Dissertations
