subject:(ERK2)

Texas A&M University

1. Alcantara, Lyonna Francesca. Role of Extracellular Regulated Kinase 2 Within Lateral Habenula in Mediating Antidepressant Response and Resilience During Adolescence.

Degree: PhD, Psychology, 2018, Texas A&M University

URL: http://hdl.handle.net/1969.1/174037

► Approximately 13% of children aged 12-17 are diagnosed with major depressive disorder (MDD). This is particularly troubling since according to the World Health Organization, suicide… (more)

▼ Approximately 13% of children aged 12-17 are diagnosed with major depressive disorder (MDD). This is particularly troubling since according to the World Health Organization, suicide is the second leading cause of death in individuals aged 15-29, suggesting that there is much left to be understood about the underlying neurocircuitry regulating symptoms of MDD. Previous work has shown that extracellular regulated kinase 2 (ERK2) activity in mesolimbic reward structures such as the ventral tegmental area (VTA), is important in mediating stress- and antidepressantresponding. The VTA receives regulatory input from the lateral habenula (LHb) however little is known about how ERK2 is expressed in the LHb after stress. To better understand this mechanism, rt-PCR, used to assess changes in mRNA, and western blot, used for protein analysis, was done for ERK2 and showed that both mRNA and protein levels of ERK2 in the LHB were modulated after stress or antidepressant exposure. To assess if ERK2 modulation could buffer stress-induced deficits, adolescent rats were given micro infusions of wtERK2 to increase ERK2 expression in the LHb, and then exposed to the stress and anxiety-eliciting tasks. Increasing ERK2 in the LHb, through a viral-mediated approach, promoted antidepressant-like responses as seen through increased time spent in the open arms of the elevated plus maze and less time immobile in the forced swim test. A separate group of rats was placed through chronic unpredictable stress and then received site-specific infusions of wtERK2 prior to behavioral testing, in an attempt to reverse stress-induced deficits. Similar to infusions in naïve animals, increasing ERK2 in the LHb was sufficient to promote antidepressant-like responses, when compared to GFP-exposed rats. This data suggests that increasing ERK2 in the LHb promotes resilience to stress and can reverse stress-induced deficits. Overall this data highlights the importance of LHb second-messenger signaling in mediating resilience to stress-eliciting stimuli. Advisors/Committee Members: Bolanos-Guzman, Carlos A (advisor), Lench, Heather (committee member), Hook, Michelle (committee member), Maren, Stephen (committee member).

Subjects/Keywords: Stress; lateral habenula; erk2

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Alcantara, L. F. (2018). Role of Extracellular Regulated Kinase 2 Within Lateral Habenula in Mediating Antidepressant Response and Resilience During Adolescence. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/174037

Chicago Manual of Style (16^th Edition):

Alcantara, Lyonna Francesca. “Role of Extracellular Regulated Kinase 2 Within Lateral Habenula in Mediating Antidepressant Response and Resilience During Adolescence.” 2018. Doctoral Dissertation, Texas A&M University. Accessed April 16, 2021. http://hdl.handle.net/1969.1/174037.

MLA Handbook (7^th Edition):

Alcantara, Lyonna Francesca. “Role of Extracellular Regulated Kinase 2 Within Lateral Habenula in Mediating Antidepressant Response and Resilience During Adolescence.” 2018. Web. 16 Apr 2021.

Vancouver:

Alcantara LF. Role of Extracellular Regulated Kinase 2 Within Lateral Habenula in Mediating Antidepressant Response and Resilience During Adolescence. [Internet] [Doctoral dissertation]. Texas A&M University; 2018. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/1969.1/174037.

Council of Science Editors:

Alcantara LF. Role of Extracellular Regulated Kinase 2 Within Lateral Habenula in Mediating Antidepressant Response and Resilience During Adolescence. [Doctoral Dissertation]. Texas A&M University; 2018. Available from: http://hdl.handle.net/1969.1/174037

King Abdullah University of Science and Technology

2. Alharbi, Siba I. A Comparative DNA Binding Study of the Human MAPK ERK2 and the Plant MAPK MPK4.

Degree: Biological and Environmental Sciences and Engineering (BESE) Division, 2020, King Abdullah University of Science and Technology

URL: http://hdl.handle.net/10754/664480

► Mitogen-activated protein kinases (MAPKs) are an important subfamily of protein kinases that are well conserved in all eukaryotes. MAPKs are the final component of a… (more)

▼ Mitogen-activated protein kinases (MAPKs) are an important subfamily of protein kinases that are well conserved in all eukaryotes. MAPKs are the final component of a three-tiered signaling module that regulates the activation of various essential cellular responses. They activate most of their substrates through catalyzing their phosphorylation. However, emerging evidence reveals that some MAPKs also possess non-catalytic functions. In particular, the human MAPK ERK2 can bind to DNA directly and mediate gene expression. The mechanism by which ERK2 binds to DNA is still unclear. In this work, we combined structural, biophysical and biochemical methods to confirm DNA binding by ERK2 and to investigate whether ERK2’s closest plant homolog MPK4 also binds to DNA. First, we identified a possible ERK2-like DNA consensus motif in plant MAPKs. We found that several plant MAPKs, including MPK4, harbor a basic motif (KARK/R or ARR/K) in a region corresponding to the ERK2 KAR motif reported to mediate DNA binding. Next, we determined the DNA binding affinity of ERK2 and MPK4 to different DNA fragments and found that MPK4 associated directly with DNA in vitro, albeit with a significantly lower affinity than did ERK2. Moreover, we observed that ERK2 and MPK4 showed preferred binding to different DNA sequences. Site-directed mutagenesis on the proposed DNA binding region of MPK4 greatly weakened DNA binding, confirming that MPK4 and ERK2 use the same structural elements to associate with DNA. Phosphorylation of the MAPKs through an upstream MKK affected the DNA binding capacity for both ERK2 and MPK4, although the effects differed. Lastly, we observed that a MPK4 mutant with a constitutively increased catalytic affinity displayed a markedly stronger DNA binding affinity compared to wild type MPK4 and phosphorylated MPK4. By demonstrating that the plant MPK4 associated with DNA in vitro, and that this association can be modified by phosphorylation and mutations, we open the possibility of additional kinase-independent functions in plant MAPKs. Advisors/Committee Members: Arold, Stefan T. (advisor), Hirt, Heribert (committee member), Al-Babili, Salim (committee member).

Subjects/Keywords: MAPK; MPK4; ERK2; DNA Binding

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Alharbi, S. I. (2020). A Comparative DNA Binding Study of the Human MAPK ERK2 and the Plant MAPK MPK4. (Thesis). King Abdullah University of Science and Technology. Retrieved from http://hdl.handle.net/10754/664480

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Alharbi, Siba I. “A Comparative DNA Binding Study of the Human MAPK ERK2 and the Plant MAPK MPK4.” 2020. Thesis, King Abdullah University of Science and Technology. Accessed April 16, 2021. http://hdl.handle.net/10754/664480.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Alharbi, Siba I. “A Comparative DNA Binding Study of the Human MAPK ERK2 and the Plant MAPK MPK4.” 2020. Web. 16 Apr 2021.

Vancouver:

Alharbi SI. A Comparative DNA Binding Study of the Human MAPK ERK2 and the Plant MAPK MPK4. [Internet] [Thesis]. King Abdullah University of Science and Technology; 2020. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/10754/664480.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Alharbi SI. A Comparative DNA Binding Study of the Human MAPK ERK2 and the Plant MAPK MPK4. [Thesis]. King Abdullah University of Science and Technology; 2020. Available from: http://hdl.handle.net/10754/664480

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Rice University

3. Misiura, Nikita. Theoretical Studies of Protein-Protein Interactions.

Degree: PhD, Natural Sciences, 2020, Rice University

URL: http://hdl.handle.net/1911/108400

► Proteins are known to play major roles in most processes taking place inside living cells. Understanding their functions and mechanisms of their action is one… (more)

▼ Proteins are known to play major roles in most processes taking place inside living cells. Understanding their functions and mechanisms of their action is one of the most important problems in the fields of biochemistry and biophysics. In this work we study a kinase called Extracellular Signal Regulated Kinase 2 (ERK2), which regulates cell cell growth, adhesion, survival and differentiation, and motor protein kinesin-1. First part of this thesis is devoted to a study of ERK2-EtsΔ138 system using variety of techniques from theoretical methods, e.g. First Passage Processes method, to Molecular Dynamics and Brownian Dynamics simulations. We first gain insights into the structure of the ERK2-EtsΔ138 complex. We find that in the lowest energy complex F120 residue of EtsΔ138 occupies ψ2 hydrophobic pocket of the FRS of ERK2 and that helix H0 of EtsΔ138 is destabilized by interaction with ERK2. We then show that in the ERK2 regulation network simultaneous decrease of strengths of all interactions can lead to both decrease or increase of overall activity of ERK2 and therefore there is an optimal strength of interactions that maximizes activity. We then formulate hypothesis that one of the binding sites of ERK2 serves to accelerate protein-protein association. We use theoretical methods and simulations to show that additional binding site can accelerate association of ERK2 and EtsΔ138 by a factors from 3 to 4. The last chapter of this thesis is dedicated to the study of Hereditary Spastic Paraplegia (HSP) which is caused by mutations in neuronal kinesin-1. HSP is a disease that is thought to be caused by slowed intracellular transport by mutated kinesin-1. Two mutations, namely N256S and R280C, were experimentally shown to decrease kinesin's velocity as well as its processivity. We used structure-based Molecular Dynamic simulations to show that these mutations can lead to increased probability of open state of ATP-binding pocket of kinesin, which in its turn can lead to low velocity due to poor catalysis. We also show that in the case of N256S mutation this effect is caused by disruption of interactions between α-helix and switch I and loop L11 of kinesin. Advisors/Committee Members: Kolomeisky, Anatoly B. (advisor).

Subjects/Keywords: ERK2; kinesin-1; IDP; Intrinsically Disordered Proteins

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Misiura, N. (2020). Theoretical Studies of Protein-Protein Interactions. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/108400

Chicago Manual of Style (16^th Edition):

Misiura, Nikita. “Theoretical Studies of Protein-Protein Interactions.” 2020. Doctoral Dissertation, Rice University. Accessed April 16, 2021. http://hdl.handle.net/1911/108400.

MLA Handbook (7^th Edition):

Misiura, Nikita. “Theoretical Studies of Protein-Protein Interactions.” 2020. Web. 16 Apr 2021.

Vancouver:

Misiura N. Theoretical Studies of Protein-Protein Interactions. [Internet] [Doctoral dissertation]. Rice University; 2020. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/1911/108400.

Council of Science Editors:

Misiura N. Theoretical Studies of Protein-Protein Interactions. [Doctoral Dissertation]. Rice University; 2020. Available from: http://hdl.handle.net/1911/108400

4. Klüßendorf, Thies. Development of a FRET-Based Fluorescent Biosensor for ERK2 Activity.

Degree: 2011, Technische Universität Dortmund

URL: http://hdl.handle.net/2003/28350

► Die dynamischen Eigenschaften von biologischen Systemen sind das Ergebnis der zugrundliegenden dynamischen Wechselbeziehungen der individuellen Komponenten. Die Mitogen-Activated Protein Kinase (MAPK)-Kaskade ist ein evolutionär konserviertes… (more)

▼ Die dynamischen Eigenschaften von biologischen Systemen sind das Ergebnis der zugrundliegenden dynamischen Wechselbeziehungen der individuellen Komponenten. Die Mitogen-Activated Protein Kinase (MAPK)-Kaskade ist ein evolutionär konserviertes Signalweiterleitungsmodul, das das Schicksal von Zellen wie Wachstum oder Differenzierung reguliert. Die Aktivierung von Extracellular Signal-Regulated Kinase 2 (ERK2) folgt einer komplexen zeitlichen und räumlichen Dynamik, die eine wichtige Rolle für bestimmte nachgeordnete Signaleffekte spielt. Eine der Hauptherausforderungen für das Verständnis von MAPK Signalweiterleitung und der Mechanismen, die Signalweiterleitung innerhalb der Zelle ermöglichen, ist der Mangel an Methoden um Kinase-Aktivität mit hoher zeitlicher und räumlicher Auflösung in lebenden Zellen zu erfassen. Während traditionelle, biochemische Methoden auf Messungen von Durchschnittswerten aus einer Vielzahl von Zellen begrenzt sind, haben bereits veröffentlichte, auf FRET basierende Biosensoren für ERK2-Aktivität mehrere schwere Nachteile wie die nur indirekte Ermittlung von ERK2-Aktivität über die Phosphorylierung eines Substrats oder über eine Konformationsänderung, einen niedrigen, dynamischen Messbereich und ungenügende räumliche Auflösung (Fujioka et al., 2006; Sato et al., 2007; Harvey et al., 2008a). Deshalb wurde in der vorliegenden Arbeit eine Methode entwickelt, um ERK2-Aktivität in einzelnen Zellen mit hoher zeitlicher und räumlicher Auflösung und einem grossen dynamischen Messbereich sichtbar zu machen und zu quantifizieren. Der direkteste Ansatz um Kinase-Aktivität in lebenden Zellen zu messen ist die Sichtbarmachung von kurzlebigen Enzym-Substrat (ES) Wechselwirkungen. Die Bildung eines ES-Komplexes kann über die Messung von Förster-Resonanzenergietransfer/ Fluoreszenzlebenszeiten (FRET/FLIM) zwischen einer Donor-markierten Kinase und einem Akzeptor-markierten Substratpeptid nachgewiesen werden (Yudushkin et al., 2007). Allerdings sind FLIM-Methoden auf ein grossen Anteil an Donormolekülen angewiesen, die FRET eingehen (d.h. einen hohen Anteil an Enzym im Komplex mit seinem Substrat) und kurze Peptide aus bekannten ERK2-Substraten haben KM-Werte in einem Bereich von 100 μM - 1 mM. Es ist deshalb schwierig, ausreichend hohe Substratkonzentration innerhalb von Zellen zu erreichen. In einem Versuch, die lokale Substratkonzentration zu erhöhen, wurde das Substratpeptid über einen flexiblen Peptidlinker mit ERK2 verbunden. Der Aufbau von ERK2 Activity Sensor 4 (EAS4) sollte prinzipiell auf alle Kinasen anwendbar sein. Er basiert auf der reversiblen Bindung und Phosphorylierung eines kurzen Substratpeptids durch die untersuchte Kinase. Die Bindung des Substratpeptids im aktiven Zentrum der Kinase verursacht eine umfassende Konformationsänderung von EAS4, die über eine Änderung des FRET-Signals erfasst werden kann, das durch Anhängen eines FRET-Paares fluoreszierender Protein erzielt wird. Deshalb ist dieser neu entwickelte, auf FRET basierende, fluoreszierende ERK2-Biosensor der Erste, der direkte… Advisors/Committee Members: Bastiaens, Philippe I. H..

Subjects/Keywords: Biosensor; ERK2; ES-Imaging; FRET; signal transduction; 570

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Klüßendorf, T. (2011). Development of a FRET-Based Fluorescent Biosensor for ERK2 Activity. (Thesis). Technische Universität Dortmund. Retrieved from http://hdl.handle.net/2003/28350

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Klüßendorf, Thies. “Development of a FRET-Based Fluorescent Biosensor for ERK2 Activity.” 2011. Thesis, Technische Universität Dortmund. Accessed April 16, 2021. http://hdl.handle.net/2003/28350.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Klüßendorf, Thies. “Development of a FRET-Based Fluorescent Biosensor for ERK2 Activity.” 2011. Web. 16 Apr 2021.

Vancouver:

Klüßendorf T. Development of a FRET-Based Fluorescent Biosensor for ERK2 Activity. [Internet] [Thesis]. Technische Universität Dortmund; 2011. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/2003/28350.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Klüßendorf T. Development of a FRET-Based Fluorescent Biosensor for ERK2 Activity. [Thesis]. Technische Universität Dortmund; 2011. Available from: http://hdl.handle.net/2003/28350

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

5. Klüßendorf, Thies. Development of a FRET-Based Fluorescent Biosensor for ERK2 Activity.

Degree: 2011, Technische Universität Dortmund

URL: http://dx.doi.org/10.17877/DE290R-9239

► Die dynamischen Eigenschaften von biologischen Systemen sind das Ergebnis der zugrundliegenden dynamischen Wechselbeziehungen der individuellen Komponenten. Die Mitogen-Activated Protein Kinase (MAPK)-Kaskade ist ein evolutionär konserviertes… (more)

▼ Die dynamischen Eigenschaften von biologischen Systemen sind das Ergebnis der zugrundliegenden dynamischen Wechselbeziehungen der individuellen Komponenten. Die Mitogen-Activated Protein Kinase (MAPK)-Kaskade ist ein evolutionär konserviertes Signalweiterleitungsmodul, das das Schicksal von Zellen wie Wachstum oder Differenzierung reguliert. Die Aktivierung von Extracellular Signal-Regulated Kinase 2 (ERK2) folgt einer komplexen zeitlichen und räumlichen Dynamik, die eine wichtige Rolle für bestimmte nachgeordnete Signaleffekte spielt. Eine der Hauptherausforderungen für das Verständnis von MAPK Signalweiterleitung und der Mechanismen, die Signalweiterleitung innerhalb der Zelle ermöglichen, ist der Mangel an Methoden um Kinase-Aktivität mit hoher zeitlicher und räumlicher Auflösung in lebenden Zellen zu erfassen. Während traditionelle, biochemische Methoden auf Messungen von Durchschnittswerten aus einer Vielzahl von Zellen begrenzt sind, haben bereits veröffentlichte, auf FRET basierende Biosensoren für ERK2-Aktivität mehrere schwere Nachteile wie die nur indirekte Ermittlung von ERK2-Aktivität über die Phosphorylierung eines Substrats oder über eine Konformationsänderung, einen niedrigen, dynamischen Messbereich und ungenügende räumliche Auflösung (Fujioka et al., 2006; Sato et al., 2007; Harvey et al., 2008a). Deshalb wurde in der vorliegenden Arbeit eine Methode entwickelt, um ERK2-Aktivität in einzelnen Zellen mit hoher zeitlicher und räumlicher Auflösung und einem grossen dynamischen Messbereich sichtbar zu machen und zu quantifizieren. Der direkteste Ansatz um Kinase-Aktivität in lebenden Zellen zu messen ist die Sichtbarmachung von kurzlebigen Enzym-Substrat (ES) Wechselwirkungen. Die Bildung eines ES-Komplexes kann über die Messung von Förster-Resonanzenergietransfer/ Fluoreszenzlebenszeiten (FRET/FLIM) zwischen einer Donor-markierten Kinase und einem Akzeptor-markierten Substratpeptid nachgewiesen werden (Yudushkin et al., 2007). Allerdings sind FLIM-Methoden auf ein grossen Anteil an Donormolekülen angewiesen, die FRET eingehen (d.h. einen hohen Anteil an Enzym im Komplex mit seinem Substrat) und kurze Peptide aus bekannten ERK2-Substraten haben KM-Werte in einem Bereich von 100 μM - 1 mM. Es ist deshalb schwierig, ausreichend hohe Substratkonzentration innerhalb von Zellen zu erreichen. In einem Versuch, die lokale Substratkonzentration zu erhöhen, wurde das Substratpeptid über einen flexiblen Peptidlinker mit ERK2 verbunden. Der Aufbau von ERK2 Activity Sensor 4 (EAS4) sollte prinzipiell auf alle Kinasen anwendbar sein. Er basiert auf der reversiblen Bindung und Phosphorylierung eines kurzen Substratpeptids durch die untersuchte Kinase. Die Bindung des Substratpeptids im aktiven Zentrum der Kinase verursacht eine umfassende Konformationsänderung von EAS4, die über eine Änderung des FRET-Signals erfasst werden kann, das durch Anhängen eines FRET-Paares fluoreszierender Protein erzielt wird. Deshalb ist dieser neu entwickelte, auf FRET basierende, fluoreszierende … Advisors/Committee Members: Bastiaens, Philippe I. H. (advisor), Wehner, Frank (referee).

Subjects/Keywords: Biosensor; ERK2; FRET; ES-Imaging; signal transduction; 570

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Klüßendorf, T. (2011). Development of a FRET-Based Fluorescent Biosensor for ERK2 Activity. (Doctoral Dissertation). Technische Universität Dortmund. Retrieved from http://dx.doi.org/10.17877/DE290R-9239

Chicago Manual of Style (16^th Edition):

Klüßendorf, Thies. “Development of a FRET-Based Fluorescent Biosensor for ERK2 Activity.” 2011. Doctoral Dissertation, Technische Universität Dortmund. Accessed April 16, 2021. http://dx.doi.org/10.17877/DE290R-9239.

MLA Handbook (7^th Edition):

Klüßendorf, Thies. “Development of a FRET-Based Fluorescent Biosensor for ERK2 Activity.” 2011. Web. 16 Apr 2021.

Vancouver:

Klüßendorf T. Development of a FRET-Based Fluorescent Biosensor for ERK2 Activity. [Internet] [Doctoral dissertation]. Technische Universität Dortmund; 2011. [cited 2021 Apr 16]. Available from: http://dx.doi.org/10.17877/DE290R-9239.

Council of Science Editors:

Klüßendorf T. Development of a FRET-Based Fluorescent Biosensor for ERK2 Activity. [Doctoral Dissertation]. Technische Universität Dortmund; 2011. Available from: http://dx.doi.org/10.17877/DE290R-9239

Florida International University

6. Rodriguez, Marbelys. Two Adaptation Mechanisms Regulate Cellular Migration in Dictyostelium discouideum.

Degree: PhD, Biology, 2014, Florida International University

URL: https://digitalcommons.fiu.edu/etd/1144 ; 10.25148/etd.FI14040813 ; FI14040813

► Dictyostelium discoideum is a simple model widely used to study many cellular functions, including differentiation, gene regulation, cellular trafficking and directional migration. Adaptation mechanisms… (more)

▼ Dictyostelium discoideum is a simple model widely used to study many cellular functions, including differentiation, gene regulation, cellular trafficking and directional migration. Adaptation mechanisms are essential in the regulation of these cellular processes. The misregulation of adaptation components often results in persistent activation of signaling pathways and aberrant cellular responses. Studying adaptation mechanisms regulating cellular migration will be crucial in the treatment of many pathological conditions in which motility plays a central role, such as tumor metastasis and acute inflammation. I will describe two adaptation mechanisms regulating directional migration in Dictyostelium cells. The Extracellular signal Regulated Kinase 2 (ERK2) plays an essential role in Dictyostelium cellular migration. ERK2 stimulates intracellular cAMP accumulation in chemotaxing cells. Aberrant ERK2 regulation results in aberrant cAMP levels and defective directional migration. The MAP Phosphatase with Leucine-rich repeats (MPL1) is crucial for ERK2 adaptation. Cells lacking, MPL1 (mpl1^- cells) displayed higher pre-stimulus and persistent post-stimulus ERK2 phosphorylation, defective cAMP production and reduced cellular migration. Reintroduction of a full length Mpl1 into mpl1^- cells restored aggregation, ERK2 regulation, random and directional motility, and cAMP production similar to wild type cells (Wt). These results suggest Mpl1 is essential for proper regulation of ERK2 phosphorylation and optimal motility in Dictyostelium cells. Cellular polarization in Dictyostelium cells in part is regulated by the activation of the AGC-related kinase Protein Kinase Related B1 (PKBR1). The PP2A regulatory subunit, B56, and the Glycogen Synthase Kinase 3 (GSK3) are necessary for PKBR1 adaptation in Dictyostelium cells. Cells lacking B56, psrA^-cells, exhibited high basal and post-stimulus persistent phosphorylation of PKBR1, increased phosphorylation of PKBR1 substrates, and aberrant motility. PKBR1 adaptation is also regulated by the GSK3. When the levels of active GSK3 are reduced in Wt and psrA^- cells, high basal levels of phosphorylated PKBR1 were observed, in a Ras dependent, but B56 independent mechanism. Altogether, PKBR1 adaptation is regulated by at least two independent mechanisms: one by GSK3 and another by PP2A/B56. Advisors/Committee Members: Dr. Lou W. Kim, Dr. Lidia Kos, Dr. Alejandro Barbieri, Dr. Ophelia Weeks, Dr. Xiaotang Wang.

Subjects/Keywords: Motility; Dictyostelium; PKBR1; B56; PP2A; Adaptation; MPL1; ERK2; Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Rodriguez, M. (2014). Two Adaptation Mechanisms Regulate Cellular Migration in Dictyostelium discouideum. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/1144 ; 10.25148/etd.FI14040813 ; FI14040813

Chicago Manual of Style (16^th Edition):

Rodriguez, Marbelys. “Two Adaptation Mechanisms Regulate Cellular Migration in Dictyostelium discouideum.” 2014. Doctoral Dissertation, Florida International University. Accessed April 16, 2021. https://digitalcommons.fiu.edu/etd/1144 ; 10.25148/etd.FI14040813 ; FI14040813.

MLA Handbook (7^th Edition):

Rodriguez, Marbelys. “Two Adaptation Mechanisms Regulate Cellular Migration in Dictyostelium discouideum.” 2014. Web. 16 Apr 2021.

Vancouver:

Rodriguez M. Two Adaptation Mechanisms Regulate Cellular Migration in Dictyostelium discouideum. [Internet] [Doctoral dissertation]. Florida International University; 2014. [cited 2021 Apr 16]. Available from: https://digitalcommons.fiu.edu/etd/1144 ; 10.25148/etd.FI14040813 ; FI14040813.

Council of Science Editors:

Rodriguez M. Two Adaptation Mechanisms Regulate Cellular Migration in Dictyostelium discouideum. [Doctoral Dissertation]. Florida International University; 2014. Available from: https://digitalcommons.fiu.edu/etd/1144 ; 10.25148/etd.FI14040813 ; FI14040813

University of Texas – Austin

7. Rainey, Mark Allan. A structure/function analysis of macromolecular recognition by the protein kinase ERK2.

Degree: PhD, Molecular Biology, 2004, University of Texas – Austin

URL: http://hdl.handle.net/2152/1392

► Mitogen-activate protein kinases (MAPKs) phosphorylate protein substrates in the presence of magnesium and adenosine triphosphate in response to extracellular environmental signals to carry out signal-dependent… (more)

▼ Mitogen-activate protein kinases (MAPKs) phosphorylate protein substrates in the presence of magnesium and adenosine triphosphate in response to extracellular environmental signals to carry out signal-dependent intracellular responses. Extracellular signal-regulated protein kinase 2 (ERK2), a member of the MAPK family, mediates cellular growth, differentiation, and proliferation in response to growth factors. Understanding the mechanism by which MAPKs specifically recognize their protein substrates to carry out phosphoryl-transfer on specific residues within these macromolecules is critical for understanding the mechanism of signal transduction fidelity. Phage display was carried out against the active form of ERK2 to find novel ERK2-binding peptides. One peptide, KKKIRCIRGWTKDIRTLADSCQY, inhibited ERK2 phosphorylation of the protein substrate Ets∆138, exhibiting competitive and mixed inhibition towards Ets∆138 (Ki = 20.7 ± 5.5 µM) and MgATP2-, respectively. Steady-state kinetics combined with a novel fluorescence anisotropy binding assay were used to quantitatively elucidate the roles of several proposed ERK2 exosites in forming a macromolecular docking complex with Ets∆138 required for efficient phosphorylation. An ERK2–Ets∆138 docking complex (Kd of 6.6 ± 1.2 µM) was shown to form independent of the substrate phospho-acceptor. Docking motif peptides proposed to bind ERK2 exosites could dissociate the ERK2–Ets∆138 docking complex, however, dissociation did not occur using a peptide containing an ERK2 phospho-acceptor indicating the lack of active site interactions in the docking complex. Mutation of ERK2 residues Lys-229 and His-230 to p38 MAPKα-like residues, an enzyme that does not efficiently phosphorylate Ets∆138, led to a 20-fold decrease in the specificity constant (kcat/Km) of Ets∆138 phosphorylation largely due to its inability to bind Ets∆138. This structure/function analysis offers a quantitative approach towards understanding the molecular determinants of protein substrate recognition by a protein kinase prior to phosphorylation. Advisors/Committee Members: Dalby, Kevin N. (advisor).

Subjects/Keywords: Protein kinase ERK2; Protein binding

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Rainey, M. A. (2004). A structure/function analysis of macromolecular recognition by the protein kinase ERK2. (Doctoral Dissertation). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/1392

Chicago Manual of Style (16^th Edition):

Rainey, Mark Allan. “A structure/function analysis of macromolecular recognition by the protein kinase ERK2.” 2004. Doctoral Dissertation, University of Texas – Austin. Accessed April 16, 2021. http://hdl.handle.net/2152/1392.

MLA Handbook (7^th Edition):

Rainey, Mark Allan. “A structure/function analysis of macromolecular recognition by the protein kinase ERK2.” 2004. Web. 16 Apr 2021.

Vancouver:

Rainey MA. A structure/function analysis of macromolecular recognition by the protein kinase ERK2. [Internet] [Doctoral dissertation]. University of Texas – Austin; 2004. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/2152/1392.

Council of Science Editors:

Rainey MA. A structure/function analysis of macromolecular recognition by the protein kinase ERK2. [Doctoral Dissertation]. University of Texas – Austin; 2004. Available from: http://hdl.handle.net/2152/1392

University of Toledo

8. Schroyer, April L. The Regulation of Mixed Lineage Kinase 3 by Extracellular Signal-Regulated Kinases 1 and 2 and Stress Stimuli in Colorectal and Ovarian Cancer Cells.

Degree: PhD, Biology (Cell-Molecular Biology), 2017, University of Toledo

URL: http://rave.ohiolink.edu/etdc/view?acc_num=toledo1513345931716064

► Mixed lineage kinase 3 (MLK3) is a mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K), which activates the extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun… (more)

▼ Mixed lineage kinase 3 (MLK3) is a mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K), which activates the extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 MAPK pathways. Interestingly, MLK3 can activate the ERK1/2 pathway through either kinase-dependent or -independent mechanisms; in the latter, MLK3 serves as a scaffold for transactivation of v-Raf murine sarcoma viral oncogene homolog B (B-Raf) and v-Raf-1 murine leukemia viral oncogene homolog 1 (Raf-1). MLK3 can transform NIH 3T3 cells and functions in migration and/or invasion of several human cancers. Computational studies recently suggested both MLK3 and ERK2 as master regulators of colorectal cancer (CRC) invasion. Human colorectal tumors display increased levels of reactive oxygen species (ROS) or oxidative stress, which activates both MLK3 and MAPK signaling pathways in specific cellular contexts and is important for carcinogenesis. Therefore, we examined whether MLK3 promoted a malignant phenotype in CRC cells under oxidative stress. We found a ROS- and ERK1/2-dependent phosphorylation of MLK3 in H2O2-treated human colorectal carcinoma (HCT116) cells as well as an interaction between endogenous MLK3 and both endogenous ERK1/2 and B-Raf. Active ERK1 phosphorylated kinase dead FLAG-MLK3 in vitro, whereas ERK1 phosphorylation of kinase dead FLAG-MLK3-S705A-S758A was reduced. MLK3 siRNA knockdown as well as FLAG-MLK3-S705A-S758A expression decreased both ERK1/2 activation and CRC cell invasion in H2O2-treated cells. These results suggest oxidative stress stimulates an ERK1/2-dependent phosphorylation of MLK3 on Ser705 and Ser758, which promotes MLK3-dependent B-Raf, MEK1/2, and ERK1/2 activation; this positive feedback loop (PFL) enhances the invasion of colon cancer cells. We also explored mechanisms to control the amount of MLK3 protein in cancer cells and discovered geldanamycin (GA), heat shock, and osmotic stress all reduced the abundance of endogenous MLK3 protein in ovarian cancer cells. Advisors/Committee Members: Chadee, Deborah (Committee Chair).

Subjects/Keywords: Biology; MLK3; ERK1; ERK2; B-Raf; oxidative stress; colorectal cancer; geldanamycin

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Schroyer, A. L. (2017). The Regulation of Mixed Lineage Kinase 3 by Extracellular Signal-Regulated Kinases 1 and 2 and Stress Stimuli in Colorectal and Ovarian Cancer Cells. (Doctoral Dissertation). University of Toledo. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=toledo1513345931716064

Chicago Manual of Style (16^th Edition):

Schroyer, April L. “The Regulation of Mixed Lineage Kinase 3 by Extracellular Signal-Regulated Kinases 1 and 2 and Stress Stimuli in Colorectal and Ovarian Cancer Cells.” 2017. Doctoral Dissertation, University of Toledo. Accessed April 16, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1513345931716064.

MLA Handbook (7^th Edition):

Schroyer, April L. “The Regulation of Mixed Lineage Kinase 3 by Extracellular Signal-Regulated Kinases 1 and 2 and Stress Stimuli in Colorectal and Ovarian Cancer Cells.” 2017. Web. 16 Apr 2021.

Vancouver:

Schroyer AL. The Regulation of Mixed Lineage Kinase 3 by Extracellular Signal-Regulated Kinases 1 and 2 and Stress Stimuli in Colorectal and Ovarian Cancer Cells. [Internet] [Doctoral dissertation]. University of Toledo; 2017. [cited 2021 Apr 16]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=toledo1513345931716064.

Council of Science Editors:

Schroyer AL. The Regulation of Mixed Lineage Kinase 3 by Extracellular Signal-Regulated Kinases 1 and 2 and Stress Stimuli in Colorectal and Ovarian Cancer Cells. [Doctoral Dissertation]. University of Toledo; 2017. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=toledo1513345931716064

9. Rafailidis, Petros. Ανοσοϊστοχημική μελέτη της έκφρασης της κινάσης ERK2 και των πρωτεϊνών των μεταγραφικών παραγόντων ETS-1 και φωσφορυλιωμένης STAT-1 σε διηθητικά καρκινώματα του μαστού.

Degree: 2014, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)

URL: http://hdl.handle.net/10442/hedi/41838

► Introduction: Mitogen-activated protein kinase (MAP kinase) pathways represent a cascade of phosphorylation events, including three pivotal kinases, Raf, MEK and ERK2, which have been implicated… (more)

▼ Introduction: Mitogen-activated protein kinase (MAP kinase) pathways represent a cascade of phosphorylation events, including three pivotal kinases, Raf, MEK and ERK2, which have been implicated in the pathogenesis of cancer. The aim of the present study was to investigate the expression of ERK2 kinase and its target proteins ETS-1 and phosphorylated STAT-1 in invasive breast carcinomas and their correlation with classic clinicopathological parameters and patients’ survival. ETS-1 is a transcription factor, implicated in the regulation of expression of various genes. STAT-1 is the first member of signal transducers and activators of transcription (STATs). Recent studies have demonstrated its apoptotic and anti-proliferative effect in breast cancer experimental models, therefore suggesting a tumor suppressor role.Methods: Immunohistochemistry was performed in paraffin-embedded tissue specimens from 151 invasive breast carcinomas to detect the expression of ERK2, ETS-1 and pSTAT-1 with clinicopathological parameters and patients’ survival. There was insufficient material for the detection of expression of ETS-1 protein for 2 patients. The results were statistically processed using univariate analysis (Pearson’s-chi-square test) and multivariate analysis (logistic regression or Cox proportional hazard regression model). Overall and disease-free survival distribution curves were assessed by Kaplan-Meier test and log rank statistics.Results: ERK2 immunoexpression was detected in the cytoplasm and nucleus ofcancer cells in 37.7% and 19.2% of cases, respectively. Nuclear ERK2 was inversely correlated with ER (p=0.039), whereas cytoplasmic ERK2 was more often expressed in lobular than ductal carcinomas (p=0.026). Nuclear ERK2 expression was found to be an independent prognostic factor of shortened overall survival of patients (p=0.040), while cytoplasmic ERK2 had an independent, favorable effect on both disease-free and overall survival (p<0.0001 and p=0.002, respectively). ETS-1 protein was detected in 77.9% of the cases in the cytoplasm, in 46.3% in the nucleus of the malignant cells, and in stromal fibroblasts as well. Cytoplasmic ETS-1 was inversely correlated with nuclear and histologic grade of the tumor (p=0.004 and 0.033, respectively). Stromal ETS-1 revealed a negative correlation with estrogen receptors (ER) (p=0.003) The univariate statistic analysis showed nuclear ETS-1 to be related to a shortened overall survival of the postmenopausal patients (p=0.032). pSTAT-1 protein was immunodetected in the cytoplasm and nuclei of the malignant cells (11.6% and 8.6% respectively). In premenopausal patients, cytoplasmic pSTAT-1 expression was positively correlated with stage (p=0.014) and ER (p=0.008). Univariate analysis showed that cytoplasmic pSTAT-1, in premenopausal patients, was associated with poor overall survival (p=0.048) and the phenotype of STAT-1/ER or STAT-1/PR co-expression was associated with shorter disease-free survival (p=0.012). On the contrary, in postmenopausal patients no association with…

Subjects/Keywords: Ανοσοϊστοχημική μελέτη; Διηθητικός καρκίνος μαστού; Immunohistochemical study; Invasive breast cancer; ETS-1; PSTA-1; ERK2

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APA (6^th Edition):

Rafailidis, P. (2014). Ανοσοϊστοχημική μελέτη της έκφρασης της κινάσης ERK2 και των πρωτεϊνών των μεταγραφικών παραγόντων ETS-1 και φωσφορυλιωμένης STAT-1 σε διηθητικά καρκινώματα του μαστού. (Thesis). National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Retrieved from http://hdl.handle.net/10442/hedi/41838

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Rafailidis, Petros. “Ανοσοϊστοχημική μελέτη της έκφρασης της κινάσης ERK2 και των πρωτεϊνών των μεταγραφικών παραγόντων ETS-1 και φωσφορυλιωμένης STAT-1 σε διηθητικά καρκινώματα του μαστού.” 2014. Thesis, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Accessed April 16, 2021. http://hdl.handle.net/10442/hedi/41838.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Rafailidis, Petros. “Ανοσοϊστοχημική μελέτη της έκφρασης της κινάσης ERK2 και των πρωτεϊνών των μεταγραφικών παραγόντων ETS-1 και φωσφορυλιωμένης STAT-1 σε διηθητικά καρκινώματα του μαστού.” 2014. Web. 16 Apr 2021.

Vancouver:

Rafailidis P. Ανοσοϊστοχημική μελέτη της έκφρασης της κινάσης ERK2 και των πρωτεϊνών των μεταγραφικών παραγόντων ETS-1 και φωσφορυλιωμένης STAT-1 σε διηθητικά καρκινώματα του μαστού. [Internet] [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2014. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/10442/hedi/41838.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Rafailidis P. Ανοσοϊστοχημική μελέτη της έκφρασης της κινάσης ERK2 και των πρωτεϊνών των μεταγραφικών παραγόντων ETS-1 και φωσφορυλιωμένης STAT-1 σε διηθητικά καρκινώματα του μαστού. [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2014. Available from: http://hdl.handle.net/10442/hedi/41838

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

McMaster University

10. Athar, Mohammad S. Characterization of ERK2 as a Transcriptional Repressor of Growth Arrest Specific Genes.

Degree: MSc, 2011, McMaster University

URL: http://hdl.handle.net/11375/10969

►

The study of growth arrest specific (GAS) genes is critical for our understanding of quiescence cell states. C/EBP-β is a transcriptional activator which is… (more)

Subjects/Keywords: ERK2; p20K; Quiescence; Growth Arrest; C/EBP-B; Transcription; Cell Biology; Cell Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Athar, M. S. (2011). Characterization of ERK2 as a Transcriptional Repressor of Growth Arrest Specific Genes. (Masters Thesis). McMaster University. Retrieved from http://hdl.handle.net/11375/10969

Chicago Manual of Style (16^th Edition):

Athar, Mohammad S. “Characterization of ERK2 as a Transcriptional Repressor of Growth Arrest Specific Genes.” 2011. Masters Thesis, McMaster University. Accessed April 16, 2021. http://hdl.handle.net/11375/10969.

MLA Handbook (7^th Edition):

Athar, Mohammad S. “Characterization of ERK2 as a Transcriptional Repressor of Growth Arrest Specific Genes.” 2011. Web. 16 Apr 2021.

Vancouver:

Athar MS. Characterization of ERK2 as a Transcriptional Repressor of Growth Arrest Specific Genes. [Internet] [Masters thesis]. McMaster University; 2011. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/11375/10969.

Council of Science Editors:

Athar MS. Characterization of ERK2 as a Transcriptional Repressor of Growth Arrest Specific Genes. [Masters Thesis]. McMaster University; 2011. Available from: http://hdl.handle.net/11375/10969

University of Colorado

11. Xiao, Yao. Conformational Dynamics in the Regulation of MAP Kinase, ERK2.

Degree: PhD, Chemistry & Biochemistry, 2015, University of Colorado

URL: https://scholar.colorado.edu/chem_gradetds/168

► The MAP kinase, extracellular signal-regulated kinase 2 (ERK2), is a key regulator of cell signaling. Aberrant up-regulation of ERK2 has been correlated with various… (more)

▼ The MAP kinase, extracellular signal-regulated kinase 2 (ERK2), is a key regulator of cell signaling. Aberrant up-regulation of ERK2 has been correlated with various diseases. ERK2 can be activated by MAP kinase kinases through dual phosphorylation at the activation loop. It remains a challenging question how changes in conformational dynamics contribute to kinase activation. NMR relaxation dispersion experiments were used to monitor changes in Ile, Leu, and Val (ILV) methyl motions in microsecond-millisecond timescale upon activation of ERK2. A structure-based procedure was developed to assign 13C1H3-labeled methyls, by comparing NMR distance constraints with the X-ray structure. This procedure yielded 60% of the methyl assignments in inactive and active forms of ILV 13C1H3-methyl labeled ERK2. In inactive ERK2, localized conformational dynamics was observed among methyls. Upon activation, the dynamics of assigned methyls in ERK2 were altered throughout the kinase core, including many residues in the catalytic pocket. The majority of methyls in active ERK2 fit to a single conformational exchange process, suggesting global domain motions involving interconversion between two states. A mutant of ERK2, engineered to enhance flexibility at the hinge region linking the N- and C-terminal domains, induced two-state conformational exchange throughout the kinase core. A mono-phospho-mimetic form of this mutant showed 25% of the dual-phosphorylated ERK2 activity. Thus, activation of ERK2 leads to a dramatic shift in conformational exchange, from a “tense” (T) state to a “relaxed” (R) state, likely through release of constraints at the hinge. To understand the effects on the conformational dynamics of ERK2 during catalysis and upon inhibitor binding, complexes of ERK2 with various ligands were formed. The binding of nucleotides and/or peptide substrates showed no significant perturbation to the T/R conformational equilibrium, with small enhancement of the T state population in active ERK2. In addition, differential conformational stabilization effects, which were not previously reported for ERK2, were observed upon the binding of different tight-binding inhibitors of ERK2. This thesis reports that ERK2 activation enhances microsecond-millisecond interconversion between conformers underlying different enzyme intermediates, thus linking protein dynamics to the catalytic cycle. The perturbations of conformational equilibrium by inhibitors reflect a novel allosteric mechanism in ERK2. Advisors/Committee Members: Natalie G. Ahn, Arthur Pardi, Marcelo Sousa, Johannes Rudolph, Loren Hough.

Subjects/Keywords: ERK2; MAP kinase; aberrant up-regulation; interconversion; conformation exchange; Biochemistry; Cell Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Xiao, Y. (2015). Conformational Dynamics in the Regulation of MAP Kinase, ERK2. (Doctoral Dissertation). University of Colorado. Retrieved from https://scholar.colorado.edu/chem_gradetds/168

Chicago Manual of Style (16^th Edition):

Xiao, Yao. “Conformational Dynamics in the Regulation of MAP Kinase, ERK2.” 2015. Doctoral Dissertation, University of Colorado. Accessed April 16, 2021. https://scholar.colorado.edu/chem_gradetds/168.

MLA Handbook (7^th Edition):

Xiao, Yao. “Conformational Dynamics in the Regulation of MAP Kinase, ERK2.” 2015. Web. 16 Apr 2021.

Vancouver:

Xiao Y. Conformational Dynamics in the Regulation of MAP Kinase, ERK2. [Internet] [Doctoral dissertation]. University of Colorado; 2015. [cited 2021 Apr 16]. Available from: https://scholar.colorado.edu/chem_gradetds/168.

Council of Science Editors:

Xiao Y. Conformational Dynamics in the Regulation of MAP Kinase, ERK2. [Doctoral Dissertation]. University of Colorado; 2015. Available from: https://scholar.colorado.edu/chem_gradetds/168

Georgia Tech

12. Bellott, Anne Claire. The Role of Caveolae in the Loss of ERK2 Activation in Stretched Skeletal Myotubes.

Degree: MS, Mechanical Engineering, 2004, Georgia Tech

URL: http://hdl.handle.net/1853/5075

► Skeletal muscle function is important to the human body for daily activities. Mechanical signals are critical to the maintenance of that function. Muscle diseases, such… (more)

Subjects/Keywords: Skeletal muscle; ERK2; Mechanotransduction; Caveolae; Caveolin-3

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APA (6^th Edition):

Bellott, A. C. (2004). The Role of Caveolae in the Loss of ERK2 Activation in Stretched Skeletal Myotubes. (Masters Thesis). Georgia Tech. Retrieved from http://hdl.handle.net/1853/5075

Chicago Manual of Style (16^th Edition):

Bellott, Anne Claire. “The Role of Caveolae in the Loss of ERK2 Activation in Stretched Skeletal Myotubes.” 2004. Masters Thesis, Georgia Tech. Accessed April 16, 2021. http://hdl.handle.net/1853/5075.

MLA Handbook (7^th Edition):

Bellott, Anne Claire. “The Role of Caveolae in the Loss of ERK2 Activation in Stretched Skeletal Myotubes.” 2004. Web. 16 Apr 2021.

Vancouver:

Bellott AC. The Role of Caveolae in the Loss of ERK2 Activation in Stretched Skeletal Myotubes. [Internet] [Masters thesis]. Georgia Tech; 2004. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/1853/5075.

Council of Science Editors:

Bellott AC. The Role of Caveolae in the Loss of ERK2 Activation in Stretched Skeletal Myotubes. [Masters Thesis]. Georgia Tech; 2004. Available from: http://hdl.handle.net/1853/5075

Virginia Commonwealth University

13. Christofakis, Steven. SCRIBBLE: A POTENTIAL DUAL KINASE INHIBITOR.

Degree: MS, Physiology, 2010, Virginia Commonwealth University

URL: https://doi.org/10.25772/9AGY-PE30 ; https://scholarscompass.vcu.edu/etd/72

► Extracellular signal-regulated kinases (ERKs) modulate cellular activities in response to extracellular stimuli and play important biological roles. Thus, perturbed kinase pathways induce pathological conditions, such… (more)

Subjects/Keywords: ERK6; p38-gamma; ERK2; Scribble; scaffolding protein; cell polarity; Life Sciences; Physiology

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APA (6^th Edition):

Christofakis, S. (2010). SCRIBBLE: A POTENTIAL DUAL KINASE INHIBITOR. (Thesis). Virginia Commonwealth University. Retrieved from https://doi.org/10.25772/9AGY-PE30 ; https://scholarscompass.vcu.edu/etd/72

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Christofakis, Steven. “SCRIBBLE: A POTENTIAL DUAL KINASE INHIBITOR.” 2010. Thesis, Virginia Commonwealth University. Accessed April 16, 2021. https://doi.org/10.25772/9AGY-PE30 ; https://scholarscompass.vcu.edu/etd/72.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Christofakis, Steven. “SCRIBBLE: A POTENTIAL DUAL KINASE INHIBITOR.” 2010. Web. 16 Apr 2021.

Vancouver:

Christofakis S. SCRIBBLE: A POTENTIAL DUAL KINASE INHIBITOR. [Internet] [Thesis]. Virginia Commonwealth University; 2010. [cited 2021 Apr 16]. Available from: https://doi.org/10.25772/9AGY-PE30 ; https://scholarscompass.vcu.edu/etd/72.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Christofakis S. SCRIBBLE: A POTENTIAL DUAL KINASE INHIBITOR. [Thesis]. Virginia Commonwealth University; 2010. Available from: https://doi.org/10.25772/9AGY-PE30 ; https://scholarscompass.vcu.edu/etd/72

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Virginia Commonwealth University

14. Allen, William. Scribble as a Possible Binding Partner for the MAP Kinases ERK2 and ERK6.

Degree: MS, Biochemistry, 2009, Virginia Commonwealth University

URL: https://doi.org/10.25772/GW76-VQ24 ; https://scholarscompass.vcu.edu/etd/1846

► We worked on finding a new kinase regulator to develop basic data to be used for cancer prevention. Our work found a link between three… (more)

Subjects/Keywords: Scribble; ERK2; ERK6; Binding Partners; Biochemistry, Biophysics, and Structural Biology; Life Sciences

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APA (6^th Edition):

Allen, W. (2009). Scribble as a Possible Binding Partner for the MAP Kinases ERK2 and ERK6. (Thesis). Virginia Commonwealth University. Retrieved from https://doi.org/10.25772/GW76-VQ24 ; https://scholarscompass.vcu.edu/etd/1846

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Allen, William. “Scribble as a Possible Binding Partner for the MAP Kinases ERK2 and ERK6.” 2009. Thesis, Virginia Commonwealth University. Accessed April 16, 2021. https://doi.org/10.25772/GW76-VQ24 ; https://scholarscompass.vcu.edu/etd/1846.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Allen, William. “Scribble as a Possible Binding Partner for the MAP Kinases ERK2 and ERK6.” 2009. Web. 16 Apr 2021.

Vancouver:

Allen W. Scribble as a Possible Binding Partner for the MAP Kinases ERK2 and ERK6. [Internet] [Thesis]. Virginia Commonwealth University; 2009. [cited 2021 Apr 16]. Available from: https://doi.org/10.25772/GW76-VQ24 ; https://scholarscompass.vcu.edu/etd/1846.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Allen W. Scribble as a Possible Binding Partner for the MAP Kinases ERK2 and ERK6. [Thesis]. Virginia Commonwealth University; 2009. Available from: https://doi.org/10.25772/GW76-VQ24 ; https://scholarscompass.vcu.edu/etd/1846

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

IUPUI

15. Staser, Karl W. Erk1 and Erk2 in hematopoiesis, mast cell function, and the management of Nf1-associated leukemia and tumors.

Degree: 2012, IUPUI

URL: http://hdl.handle.net/1805/2892

►

Indiana University-Purdue University Indianapolis (IUPUI)

Neurofibromatosis type 1 is a genetic disease that results from either heritable or spontaneous autosomal dominant mutations in the NF1… (more)

▼

Indiana University-Purdue University Indianapolis (IUPUI)

Neurofibromatosis type 1 is a genetic disease that results from either heritable or spontaneous autosomal dominant mutations in the NF1 gene, which encodes a protein serving, at least in part, to accelerate the intrinsic hydrolysis of active Ras-GTP to inactive Ras-GDP. A second-hit NF1 mutation precedes predominant NF1 neoplasms, including juvenile myelomoncytic leukemia (JMML) and plexiform neurofibroma formation, potentially fatal conditions with no medical therapy. While NF1 loss of heterozygosity (LOH) in myeloid progenitor cells sufficiently engenders leukemogenesis, plexiform neurofibroma formation depends on LOH in Schwann cells and Nf1 heterozygosity in the hematopoietic system. Specifically, recruited Nf1+/- mast cells accelerate tumorigenesis through secreted cytokines and growth factors. Nf1+/- mast cells depend upon deregulated signaling in c-kit pathways, a receptor system conserved in hematopoietic stem cells (HSCs). Accordingly, Nf1-/- myeloid progenitor cells, which can induce a JMML-like disease in mice, also demonstrate deregulated c-kit receptor signaling. C-kit-activated Nf1+/- mast cells and Nf1-/- myeloid progenitors both show increased latency and potency of active Erk1 and Erk2, the principal cytosolic-to-nuclear effectors of canonical Ras-Raf-Mek signaling. Thus, Erk represents a potential regulator of leukemogenesis and tumor-associated inflammation. However, single and combined Erk1 and Erk2 roles in HSC function, myelopoiesis, and mature mast cell physiology remain unknown, and recent hematopoietic studies relying on chemical Mek-Erk inhibitors have produced conflicting results. Here, we show that hematopoietic stability, myelopoiesis, and mast cell generation require Erk1 or Erk2, but individual isoforms are largely dispensable. Principally, Erk-disrupted hematopoietic stem cells incorporate BrdU but are incapable of dividing, a novel and cell type-specific Erk function. Similarly, mast cell proliferation requires Erk but cytokine production proceeds through other pathways, elucidating molecule-specific functions within the c-kit cascade. Based on these findings, we have reduced tumor mast cell infiltration by treating genetically-engineered tumor model mice with PD0325901, a preclinical Mek-Erk inhibitor. Moreover, we have devised a quadruple transgenic HSC transplantation model to examine dual Erk disruption in the context of Nf1 nullizygosity, testing whether diseased hematopoiesis requires Erk. These insights illuminate cell-specific Erk functions in normal and Nf1-deficient hematopoiesis, informing the feasibility of targeting Mek-Erk in NF1-associated disease.

Advisors/Committee Members: Clapp, D. Wade, Yang, Feng-Chun, Goebl, Mark, 1958-, Harrington, Maureen A..

Subjects/Keywords: NF1, Erk1, Erk2, mast cells, hematopoiesis, neurofibroma, leukemia; Neurofibromatosis; Nervous system – Diseases; Medical genetics; Mast cells; Hematopoiesis; Neurofibroma; Leukemia; Cytokines – Research – Methodology; Tumors – Genetic aspects

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APA (6^th Edition):

Staser, K. W. (2012). Erk1 and Erk2 in hematopoiesis, mast cell function, and the management of Nf1-associated leukemia and tumors. (Thesis). IUPUI. Retrieved from http://hdl.handle.net/1805/2892

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Staser, Karl W. “Erk1 and Erk2 in hematopoiesis, mast cell function, and the management of Nf1-associated leukemia and tumors.” 2012. Thesis, IUPUI. Accessed April 16, 2021. http://hdl.handle.net/1805/2892.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Staser, Karl W. “Erk1 and Erk2 in hematopoiesis, mast cell function, and the management of Nf1-associated leukemia and tumors.” 2012. Web. 16 Apr 2021.

Vancouver:

Staser KW. Erk1 and Erk2 in hematopoiesis, mast cell function, and the management of Nf1-associated leukemia and tumors. [Internet] [Thesis]. IUPUI; 2012. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/1805/2892.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Staser KW. Erk1 and Erk2 in hematopoiesis, mast cell function, and the management of Nf1-associated leukemia and tumors. [Thesis]. IUPUI; 2012. Available from: http://hdl.handle.net/1805/2892

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

16. Alter, Benedict. Isoform-Specific Roles of Extracellular Signal-Regulated Kinases in Pain.

Degree: PhD, Biology and Biomedical Sciences: Neurosciences, 2012, Washington University in St. Louis

URL: https://openscholarship.wustl.edu/etd/680

► ABSTRACT OF THE DISSERTATION Isoform-specific roles of Extracellular Signal-Regulated Kinases in pain by Benedict Joseph Alter Doctor of Philosophy in Biology and Biomedical Sciences Neurosciences… (more)

▼ ABSTRACT OF THE DISSERTATION Isoform-specific roles of Extracellular Signal-Regulated Kinases in pain by Benedict Joseph Alter Doctor of Philosophy in Biology and Biomedical Sciences Neurosciences Washington University in St. Louis, 2012 Professor Robert Gereau, Chairperson The extracellular signal-regulated kinase: ERK) isoforms, ERK1 and ERK2, are believed to be key signaling molecules in nociception and nociceptive sensitization. Studies utilizing inhibitors targeting the shared ERK1/2 upstream activator, mitogen-activated protein kinase kinase: MEK), and transgenic mice expressing a dominant negative form of MEK have established the importance of ERK1/2 signaling. However, these techniques do not discriminate between ERK1 and ERK2. To dissect the function of each isoform in pain, mice with a targeted genetic deletion of ERK1: ERK1-/-) and mice with a conditional deletion of ERK2 in nociceptors: ERK2f/f;NaV1.8-Cre) were used. Although both isoforms are activated: phosphorylated) following inflammation, deletion of ERK1 had no effect in several models of chemical nociception, inflammatory pain, and neuropathic pain. In contrast, conditional deletion of ERK2 in nociceptors attenuates nociceptive spontaneous behavior in the second phase of the formalin test, reduces inflammatory mechanical hypersensitivity, and eliminates heat hypersensitivity due to the inflammatory mediator, nerve growth factor: NGF). Nociceptive sensitization was not reduced in all models tested, since ERK2f/f;NaV1.8-Cre mice developed robust heat hypersensitivity to other inflammatory and chemical insults. Biochemical analysis of both lines revealed that eliminating one ERK isoform led to elevated phosphorylation of the remaining isoform at baseline, which could explain the lack of a phenotype in ERK1-/- mice. However, this is probably not the case since the elevation in spinal cord ERK2 phosphorylation above baseline following noxious stimulation is not affected by the deletion of ERK1. It is also possible that other intracellular signaling cascades may compensate for the loss of ERK1. This seems less probable since systemic MEK inhibition attenuates formalin-induced spontaneous nociceptive behaviors similarly in ERK1-/- and WT littermate controls. These experiments demonstrate an isoform-specific role for ERK2 on the behavioral level. On the cellular level, ERK2 is also partially required for innervation of the epidermis by peptidergic nociceptive afferents that express the NGF receptor, TrkA. The partial reduction in epidermal innervation is not accompanied by cell loss, suggesting a defect in axon growth or maintenance. Fiber loss is unlikely to account for all behavioral phenotypes observed in ERK2f/f;NaV1.8-Cre mice since remaining epidermal fibers have previously been shown to play important roles on the behavioral level. Additionally, ERK1-/- mice have exaggerated NGF-induced heat hypersensitivity but do not have altered epidermal innervation. Overall, these data highlight the complicated interplay between ERK1 and ERK2 in vivo and… Advisors/Committee Members: Robert Gereau.

Subjects/Keywords: Neurosciences; Biology; Medicine; ERK1; ERK2; isoform; MAPK; nociception; pain

…and ERK2 – Similarities and Differences ............................................ 26 What… …roles do ERK1 and ERK2 play in nociception and nociceptive sensitization… …31 vi Chapter 2: Genetic targeting of ERK1 suggests a predominant role for ERK2 in… …73 Chapter 3: Nociceptor ERK2 drives peripheral sensitization and is required for epidermal… …122 ERK2 is necessary for epidermal innervation in a subset of peptidergic fibers…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Alter, B. (2012). Isoform-Specific Roles of Extracellular Signal-Regulated Kinases in Pain. (Doctoral Dissertation). Washington University in St. Louis. Retrieved from https://openscholarship.wustl.edu/etd/680

Chicago Manual of Style (16^th Edition):

Alter, Benedict. “Isoform-Specific Roles of Extracellular Signal-Regulated Kinases in Pain.” 2012. Doctoral Dissertation, Washington University in St. Louis. Accessed April 16, 2021. https://openscholarship.wustl.edu/etd/680.

MLA Handbook (7^th Edition):

Alter, Benedict. “Isoform-Specific Roles of Extracellular Signal-Regulated Kinases in Pain.” 2012. Web. 16 Apr 2021.

Vancouver:

Alter B. Isoform-Specific Roles of Extracellular Signal-Regulated Kinases in Pain. [Internet] [Doctoral dissertation]. Washington University in St. Louis; 2012. [cited 2021 Apr 16]. Available from: https://openscholarship.wustl.edu/etd/680.

Council of Science Editors:

Alter B. Isoform-Specific Roles of Extracellular Signal-Regulated Kinases in Pain. [Doctoral Dissertation]. Washington University in St. Louis; 2012. Available from: https://openscholarship.wustl.edu/etd/680

Kent State University

17. Majumdar, Avijit. Regulation of the Activation and Activity of the Extra-cellular Signal Regulated Kinases 1 & 2 MAP Kinase Pathway by Eukaryotic Initiation Factor 2 Associated Glycoprotein P67.

Degree: PhD, College of Arts and Sciences / School of Biomedical Sciences, 2008, Kent State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=kent1209000031

► The eukaryotic initiation factor 2 associated glycoprotein p67 plays an important role in the regulation of global protein synthesis by modulating the phosphorylation of the… (more)

Subjects/Keywords: Biomedical Research; Cellular Biology; Molecular Biology; P67; ERK1; ERK2; Oncogenic KRasV12; Tumor suppressor

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Majumdar, A. (2008). Regulation of the Activation and Activity of the Extra-cellular Signal Regulated Kinases 1 & 2 MAP Kinase Pathway by Eukaryotic Initiation Factor 2 Associated Glycoprotein P67. (Doctoral Dissertation). Kent State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=kent1209000031

Chicago Manual of Style (16^th Edition):

Majumdar, Avijit. “Regulation of the Activation and Activity of the Extra-cellular Signal Regulated Kinases 1 & 2 MAP Kinase Pathway by Eukaryotic Initiation Factor 2 Associated Glycoprotein P67.” 2008. Doctoral Dissertation, Kent State University. Accessed April 16, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=kent1209000031.

MLA Handbook (7^th Edition):

Majumdar, Avijit. “Regulation of the Activation and Activity of the Extra-cellular Signal Regulated Kinases 1 & 2 MAP Kinase Pathway by Eukaryotic Initiation Factor 2 Associated Glycoprotein P67.” 2008. Web. 16 Apr 2021.

Vancouver:

Majumdar A. Regulation of the Activation and Activity of the Extra-cellular Signal Regulated Kinases 1 & 2 MAP Kinase Pathway by Eukaryotic Initiation Factor 2 Associated Glycoprotein P67. [Internet] [Doctoral dissertation]. Kent State University; 2008. [cited 2021 Apr 16]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=kent1209000031.

Council of Science Editors:

Majumdar A. Regulation of the Activation and Activity of the Extra-cellular Signal Regulated Kinases 1 & 2 MAP Kinase Pathway by Eukaryotic Initiation Factor 2 Associated Glycoprotein P67. [Doctoral Dissertation]. Kent State University; 2008. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=kent1209000031

Vanderbilt University

18. Mazalouskas, Matthew David. Composition, Regulation, and Function of Protein Serine/Threonine Phosphatase•Kinase Signaling Modules.

Degree: PhD, Pharmacology, 2014, Vanderbilt University

URL: http://hdl.handle.net/1803/11220

► The macromolecular assembly of protein serine/threonine phosphatase•kinase complexes mechanistically enhances the speed and fidelity of cell signaling events. These signaling modules allow for acute regulation… (more)

▼ The macromolecular assembly of protein serine/threonine phosphatase•kinase complexes mechanistically enhances the speed and fidelity of cell signaling events. These signaling modules allow for acute regulation of substrates common to both enzymes as well as intramolecular regulation of kinase activity by the associated phosphatase or vice versa. Protein serine/threonine phosphatase 2A (PP2A) interacts with calcium/calmodulin-dependent protein kinase IV (CaMKIV) and negatively regulates the activity of the kinase. A phospho-Thr200-CaMKIV antibody was utilized to monitor ionomycin-induced signal output of endogenous CaMKIV•PP2A complexes. The PP2A canonical regulatory Balpha and Bdelta subunits recruit the catalytic subunit of PP2A (PP2AC) to the kinase but do not promote dephosphorylation of the activating phospho-Thr200 site. Balpha and Bdelta subunits also recruit PP2AC to the serine/threonine kinase Raf1. In contrast to CaMKIV, PP2A positively regulates Raf1-MEK-ERK signaling by dephosphorylating the inhibitory phospho-Ser259-Raf1 residue. To better understand the regulatory mechanisms controlling ABalpha/deltaC-Raf1 interactions in response to stimuli, we coupled Reversible Cross-Link Immuno-Precipitation (ReCLIP) with mass spectrometry. Tandem affinity-purified ABdeltaC•Raf1 complexes were isolated from cells treated with a chemical crosslinking reagent to stabilize transient protein-protein interactions. Proteomic analysis of the PP2A•Raf1 complex identified several putative interacting proteins that may play a role in the regulation of this phosphatase•kinase complex. Raf1 signaling is inactivated following the dephosphorylation of phospho-Ser338 by protein serine/threonine phosphatase 5 (PP5). We monitored the binding of PP2A and PP5 to Raf1 using co-immunoprecipitation assays and found that both phosphatases concurrently associate with Raf1, which acts as the scaffold in this multiprotein complex. We also identify several novel PP5•kinase complexes whose stable interactions are facilitated by HSP90. Notably, PP5 interacts with multiple ERKs. Our studies support a novel role for PP5•ERK complexes in regulating the feedback phosphorylation of Raf1 at Ser-289, Ser-296, and/or Ser-301 and show that these PP5•ERK complexes are regulated by small G proteins. Whereas constitutively active Rac1 promotes the assembly of PP5•ERK1/2 complexes, oncogenic HRas has no effect on PP5-ERK1 binding but selectively decreases the PP5-ERK2 interaction, in a manner that is independent of PP5 and MEK activity, yet paradoxically requires ERK2 activity. Advisors/Committee Members: Brian Wadzinski (committee member), Albert Reynolds (committee member), BethAnn McLaughlin (committee member), Claus Schneider (committee member), Vsevolod Gurevich (Committee Chair).

Subjects/Keywords: Raf; Raf1; CaMKIV; phosphatase; PP2A; PP5; Rac; Ras; S100; S100B; S100A1; ERK2; ERK1; ERK; signaling; small G protein; kinase; MAPK; MEK; feedback; phosphorylation; C-Raf; CRaf; ERK1b; ERK1c; cancer; RASopathy; HRas; KRas

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mazalouskas, M. D. (2014). Composition, Regulation, and Function of Protein Serine/Threonine Phosphatase•Kinase Signaling Modules. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/11220

Chicago Manual of Style (16^th Edition):

Mazalouskas, Matthew David. “Composition, Regulation, and Function of Protein Serine/Threonine Phosphatase•Kinase Signaling Modules.” 2014. Doctoral Dissertation, Vanderbilt University. Accessed April 16, 2021. http://hdl.handle.net/1803/11220.

MLA Handbook (7^th Edition):

Mazalouskas, Matthew David. “Composition, Regulation, and Function of Protein Serine/Threonine Phosphatase•Kinase Signaling Modules.” 2014. Web. 16 Apr 2021.

Vancouver:

Mazalouskas MD. Composition, Regulation, and Function of Protein Serine/Threonine Phosphatase•Kinase Signaling Modules. [Internet] [Doctoral dissertation]. Vanderbilt University; 2014. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/1803/11220.

Council of Science Editors:

Mazalouskas MD. Composition, Regulation, and Function of Protein Serine/Threonine Phosphatase•Kinase Signaling Modules. [Doctoral Dissertation]. Vanderbilt University; 2014. Available from: http://hdl.handle.net/1803/11220

Texas Medical Center

19. Kim, Tae Kon. THE ROLE OF MAP KINASES ON THE FUNCTIONAL HETEROGENEITY OF HUMAN CD8+ T CELL MATURATION SUBSETS.

Degree: PhD, 2010, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/10

► While prior studies have focused on naïve (CD45RA+CD27+) and early stage memory (CD45RA-CD27+) CD8+ T cells, late memory CD8+ T cells (CD45RA+CD27) have received less… (more)

▼ While prior studies have focused on naïve (CD45RA+CD27+) and early stage memory (CD45RA-CD27+) CD8+ T cells, late memory CD8+ T cells (CD45RA+CD27) have received less interest because this subset of T cells is generally recognized as effectors, which produce IFNγ (but no IL-2) and perforin. However, multiple studies suggest that late memory CD8+ T cells may provide inadequate protection in infectious diseases and cancer models. To better understand the unique function of late memory CD8+ T cells, I optimized multi-color flow cytometry techniques to assess the cytokine production of each human CD8+ T cell maturation subset. I demonstrated that late memory CD8+ T cells are the predominant producer of CC chemokines (e.g. MIP-1β), but rarely produce IL-2; therefore they do not co-produce IL-2/IFNγ (polyfunctionality), which has been shown to be critical for protective immunity against chronic viral infection. These data suggest that late memory CD8+ T cells are not just cytotoxic effectors, but may have unique functional properties. Determining the molecular signature of each CD8+ T cell maturation subset will help characterize the role of late memory CD8+ T cells. Prior studies suggest that ERK1 and ERK2 play a role in cytokine production including IL-2 in T cells. Therefore, I tested whether differential expression of ERK1 and ERK2 in CD8+ T cell maturation subsets contributes to their functional signature by a novel flow cytometry technique. I found that the expression of total ERK1, but not ERK2, is significantly diminished in late memory CD8+ T cells and that ERK1 expression is strongly associated with IL-2 production and CD28 expression. I also found that IL-2 production is increased in late memory CD8+ T cells by over-expressing ERK1. Collectively, these data suggest that ERK1 is required for IL-2 production in human CD8+ T cells. In summary, this dissertation demonstrated that ERK1 is down-regulated in human late memory CD8+ T cells, leading to decreased production of IL-2. The data in this dissertation also suggested that the functional heterogeneity in human CD8+ T cell maturation subsets results from their differential ERK1 expression. Advisors/Committee Members: Krishna V. Komanduri, Bradley W. McIntyre, David McConkey.

Subjects/Keywords: Human; CD8; T cell; activation; chemokine; cytokine; ERK1; ERK2; IL-2; GVHD; Immunology and Infectious Disease; Medical Immunology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kim, T. K. (2010). THE ROLE OF MAP KINASES ON THE FUNCTIONAL HETEROGENEITY OF HUMAN CD8+ T CELL MATURATION SUBSETS. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/10

Chicago Manual of Style (16^th Edition):

Kim, Tae Kon. “THE ROLE OF MAP KINASES ON THE FUNCTIONAL HETEROGENEITY OF HUMAN CD8+ T CELL MATURATION SUBSETS.” 2010. Doctoral Dissertation, Texas Medical Center. Accessed April 16, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/10.

MLA Handbook (7^th Edition):

Kim, Tae Kon. “THE ROLE OF MAP KINASES ON THE FUNCTIONAL HETEROGENEITY OF HUMAN CD8+ T CELL MATURATION SUBSETS.” 2010. Web. 16 Apr 2021.

Vancouver:

Kim TK. THE ROLE OF MAP KINASES ON THE FUNCTIONAL HETEROGENEITY OF HUMAN CD8+ T CELL MATURATION SUBSETS. [Internet] [Doctoral dissertation]. Texas Medical Center; 2010. [cited 2021 Apr 16]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/10.

Council of Science Editors:

Kim TK. THE ROLE OF MAP KINASES ON THE FUNCTIONAL HETEROGENEITY OF HUMAN CD8+ T CELL MATURATION SUBSETS. [Doctoral Dissertation]. Texas Medical Center; 2010. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/10

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Open Access Theses and Dissertations