subject:(Protein kinases)

University of Utah

1. Tsai, I-Chun. Regulation of casein kinase I [epsilon] in non-canonical Wnt signaling;.

Degree: PhD, Oncological Sciences;, 2007, University of Utah

URL: http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/1449/rec/1088

► Casein kinase I epsilon (CKI?) and casein kinase I delta (CKI?) are members of the CKI serine/threonine protein kinase family. These two highly-related kinases are… (more)

▼ Casein kinase I epsilon (CKI?) and casein kinase I delta (CKI?) are members of the CKI serine/threonine protein kinase family. These two highly-related kinases are ubiquitously expressed in mammalian tissues and are implicated in multiple cellular processes, including Wnt signaling transduction, circadian rhythms and Hedgehog pathway. Due to the ability to induce axis duplication and to activate the TCF-dependent reporter, CKI? and CKI? were first reported as positive regulators of the Wnt?-catenin pathway. Biochemical studies in our laboratory demonstrated that CKI? could destabilize the ?-catenin destruction complex, leading to the accumulation of ?-catenin. However, CKI?; is not only involved in the Wnt/?-catenin pathway but is also required for the convergent extension (CE) movements during Xenopus development. CE comprises the morphological polarization and cell migration, regulating the formation of the body axis in a ?-catenin independent manner. Downstream of Wnt, Frizzled (Fz) receptors and Dishevelled (Dvl/Dsh) protein, CE movements can be stimulated by the activation of small GTPases, including Rho and Rac, which facilitate cytoskeleton reorganization and activate the JNK pathway. Although CKI?; activity has been shown to be important for the regulation of CE movements, the molecular mechanism by which CKI?; regulates CE movements has not been addressed yet. In order to find additional roles of CKI?; in the Wnt signaling pathway, my study focuses on understanding how CKI?; regulates CE movements and the ?-catenin-independent Wnt pathway. The characterization of CKI? and CKI? mutants demonstrates that CKI?/? participate in the control of convergent extension (CE) movements through a ?-catenin independent mechanism. Further investigation of CKI?; function uncovered a novel mechanism of CKI?, in which CKI?; activates Rap1, a monomeric GTP binding protein, through regulating the activity of a GAP (GTPase activating protein) of Rap1, E6TP1. Taken together, this dissertation extends the knowledge of CKI?/? in mediating Wnt/PCP (Planer Cell Polarity) signaling. Since the regulation of cell polarity is highly related to the regulation of cell migration and cancer metastasis, results from these studies not only deepen our understanding the CKI?;/? function in embryonic development but also may be applied for understanding of the progression of cancer development in the future.

Subjects/Keywords: Protein Kinases; Biochemistry

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APA (6^th Edition):

Tsai, I. (2007). Regulation of casein kinase I [epsilon] in non-canonical Wnt signaling;. (Doctoral Dissertation). University of Utah. Retrieved from http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/1449/rec/1088

Chicago Manual of Style (16^th Edition):

Tsai, I-Chun. “Regulation of casein kinase I [epsilon] in non-canonical Wnt signaling;.” 2007. Doctoral Dissertation, University of Utah. Accessed April 19, 2021. http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/1449/rec/1088.

MLA Handbook (7^th Edition):

Tsai, I-Chun. “Regulation of casein kinase I [epsilon] in non-canonical Wnt signaling;.” 2007. Web. 19 Apr 2021.

Vancouver:

Tsai I. Regulation of casein kinase I [epsilon] in non-canonical Wnt signaling;. [Internet] [Doctoral dissertation]. University of Utah; 2007. [cited 2021 Apr 19]. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/1449/rec/1088.

Council of Science Editors:

Tsai I. Regulation of casein kinase I [epsilon] in non-canonical Wnt signaling;. [Doctoral Dissertation]. University of Utah; 2007. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/1449/rec/1088

Columbia University

2. Taveras, Carmen D. Role of Aurora B-mediated phosphorylation during mitosis and interphase.

Degree: 2017, Columbia University

URL: https://doi.org/10.7916/D8QC08VV

► Accurate chromosome segregation requires a spindle apparatus composed of microtubules that arise from the spindle to attach to the kinetochore, a protein complex assembled at… (more)

▼ Accurate chromosome segregation requires a spindle apparatus composed of microtubules that arise from the spindle to attach to the kinetochore, a protein complex assembled at the centromere of each chromosome. Failure to segregate chromosomes accurately may lead to lethal early developmental defects and tumorigenesis. To achieve proper kinetochore binding to microtubules, mammalian cells have evolved elaborate mechanisms to correct attachment errors and stabilize correct ones. Current models suggest that tension between kinetochore pairs (inter-kinetochore stretch) and tension at the kinetochore (intra-kinetochore stretch) produces a spatial separation of Aurora B kinase from kinetochore-associated and microtubule-binding substrates, subsequently reducing their phosphorylations and increasing their microtubule affinity. However, the tension-based models do not explain how the initial microtubule binding at unattached kinetochores occurs, where there is no tension and kinetochore-associated substrates are highly phosphorylated and, hence unable to bind to microtubules. Therefore, there must be a mechanism that explains how the phosphorylation of kinetochore substrates by Aurora B is reduced in the absence of tension. In the first part of this thesis, I examine the structural features of the coiled-coil domain of the kinetochore-associated kinesin motor protein, CENP-E. Using Single-Molecule High-Resolution Colocalization (SHREC) microscopy analysis of kinetochore-associated CENP-E, I show that CENP-E undergoes structural rearrangements prior to and after tension generation at the kinetochore. Chemical inhibition of the motor motility or genetic perturbations of the coiled-coil domain of CENP-E increases Aurora B-mediated Ndc80 phosphorylation in a tension-independent manner. Importantly, metaphase chromosome misalignment caused by inhibition of CENP-E can be rescued by chemical inhibition of Aurora B kinase. Therefore, CENP-E regulates the initial kinetochore binding to microtubules and the stabilization of kinetochore-microtubule attachments. Formin-dependent actin assembly is known to play a role in multiple processes, including cytokinesis, filopodia formation, cell polarity, and cell adhesion. Thus, formin malfunction is directly linked to various pathologies, including defects in cell migration and tumor suppression. Although the role of formins in actin polymerization has been well described, the mechanistic processes that regulate the actin assembly function of formins remain poorly understood, especially the interplay among the various sub-families of formins and how they are spatiotemporally regulated. In the second part of this thesis, I show that Aurora B-mediated phosphorylation of the formin, mDia3 regulates actin assembly. Previous studies identified two Aurora B phosphorylation sites in the FH2 domain of mDia3. To this end, phosphomimetic and non-phosphorylatable mutants of a constitutively active form of mDia3 were designed to test whether phosphorylation by Aurora B regulates actin…

Subjects/Keywords: Cytology; Protein kinases

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APA (6^th Edition):

Taveras, C. D. (2017). Role of Aurora B-mediated phosphorylation during mitosis and interphase. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/D8QC08VV

Chicago Manual of Style (16^th Edition):

Taveras, Carmen D. “Role of Aurora B-mediated phosphorylation during mitosis and interphase.” 2017. Doctoral Dissertation, Columbia University. Accessed April 19, 2021. https://doi.org/10.7916/D8QC08VV.

MLA Handbook (7^th Edition):

Taveras, Carmen D. “Role of Aurora B-mediated phosphorylation during mitosis and interphase.” 2017. Web. 19 Apr 2021.

Vancouver:

Taveras CD. Role of Aurora B-mediated phosphorylation during mitosis and interphase. [Internet] [Doctoral dissertation]. Columbia University; 2017. [cited 2021 Apr 19]. Available from: https://doi.org/10.7916/D8QC08VV.

Council of Science Editors:

Taveras CD. Role of Aurora B-mediated phosphorylation during mitosis and interphase. [Doctoral Dissertation]. Columbia University; 2017. Available from: https://doi.org/10.7916/D8QC08VV

Hong Kong University of Science and Technology

3. Wang, Xi. Stk24 promotes myogenic differentiation via multiple mechanisms.

Degree: 2011, Hong Kong University of Science and Technology

URL: http://repository.ust.hk/ir/Record/1783.1-7914 ; https://doi.org/10.14711/thesis-b1155425 ; http://repository.ust.hk/ir/bitstream/1783.1-7914/1/th_redirect.html

► Through an RNAi-based screening for kinases involved in myogenic differentiation, weidentified Stk24/MST3, a member of the mammalian Ste20 family, as a key regulator. Knockdown of… (more)

Subjects/Keywords: Myogenesis ; Protein kinases

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APA (6^th Edition):

Wang, X. (2011). Stk24 promotes myogenic differentiation via multiple mechanisms. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-7914 ; https://doi.org/10.14711/thesis-b1155425 ; http://repository.ust.hk/ir/bitstream/1783.1-7914/1/th_redirect.html

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):

Wang, Xi. “Stk24 promotes myogenic differentiation via multiple mechanisms.” 2011. Thesis, Hong Kong University of Science and Technology. Accessed April 19, 2021. http://repository.ust.hk/ir/Record/1783.1-7914 ; https://doi.org/10.14711/thesis-b1155425 ; http://repository.ust.hk/ir/bitstream/1783.1-7914/1/th_redirect.html.

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

MLA Handbook (7^th Edition):

Wang, Xi. “Stk24 promotes myogenic differentiation via multiple mechanisms.” 2011. Web. 19 Apr 2021.

Vancouver:

Wang X. Stk24 promotes myogenic differentiation via multiple mechanisms. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2011. [cited 2021 Apr 19]. Available from: http://repository.ust.hk/ir/Record/1783.1-7914 ; https://doi.org/10.14711/thesis-b1155425 ; http://repository.ust.hk/ir/bitstream/1783.1-7914/1/th_redirect.html.

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

Council of Science Editors:

Wang X. Stk24 promotes myogenic differentiation via multiple mechanisms. [Thesis]. Hong Kong University of Science and Technology; 2011. Available from: http://repository.ust.hk/ir/Record/1783.1-7914 ; https://doi.org/10.14711/thesis-b1155425 ; http://repository.ust.hk/ir/bitstream/1783.1-7914/1/th_redirect.html

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

Rutgers University

4. Fellmeth, Jessica, 1983-. Analysis of human Aurora C Kinase variants in oocyte meiosis.

Degree: PhD, Microbiology and Molecular Genetics, 2015, Rutgers University

URL: https://rucore.libraries.rutgers.edu/rutgers-lib/48487/

►

The birth of a healthy child is often a priority for couples, yet many couples will unfortunately suffer from infertility. Aneuploidy is the leading genetic… (more)

Subjects/Keywords: Protein kinases; Ovum

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APA (6^th Edition):

Fellmeth, Jessica, 1. (2015). Analysis of human Aurora C Kinase variants in oocyte meiosis. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/48487/

Chicago Manual of Style (16^th Edition):

Fellmeth, Jessica, 1983-. “Analysis of human Aurora C Kinase variants in oocyte meiosis.” 2015. Doctoral Dissertation, Rutgers University. Accessed April 19, 2021. https://rucore.libraries.rutgers.edu/rutgers-lib/48487/.

MLA Handbook (7^th Edition):

Fellmeth, Jessica, 1983-. “Analysis of human Aurora C Kinase variants in oocyte meiosis.” 2015. Web. 19 Apr 2021.

Vancouver:

Fellmeth, Jessica 1. Analysis of human Aurora C Kinase variants in oocyte meiosis. [Internet] [Doctoral dissertation]. Rutgers University; 2015. [cited 2021 Apr 19]. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/48487/.

Council of Science Editors:

Fellmeth, Jessica 1. Analysis of human Aurora C Kinase variants in oocyte meiosis. [Doctoral Dissertation]. Rutgers University; 2015. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/48487/

Hong Kong University of Science and Technology

5. Zhang, Peng. S-nitrosylation of cyclin-dependent kinase 5 and its activator p35 in neuronal morphogenesis and synaptic function.

Degree: 2013, Hong Kong University of Science and Technology

URL: http://repository.ust.hk/ir/Record/1783.1-86315 ; https://doi.org/10.14711/thesis-b1266266 ; http://repository.ust.hk/ir/bitstream/1783.1-86315/1/th_redirect.html

► Cyclin-dependent kinase 5 (Cdk5), a proline-directed serine/threonine kinase, plays important roles in various neuronal functions including neuronal migration, neurite outgrowth, synapse development, and plasticity. The… (more)

▼ Cyclin-dependent kinase 5 (Cdk5), a proline-directed serine/threonine kinase, plays important roles in various neuronal functions including neuronal migration, neurite outgrowth, synapse development, and plasticity. The dysfunction of Cdk5 activity is associated with neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Therefore, the precise regulation of Cdk5 activity is important for proper neuronal development and functioning. Unlike other cyclin-dependent kinase family members, which are regulated by cyclins, Cdk5 is activated through its association with the neuronal specific activators, p35 and p39. However, whether and how Cdk5 activity is regulated in neurons by other molecular mechanisms remain unclear. This study revealed Cdk5 and its activator p35 can undergo post-translational modification by S-nitrosylation, which involves a reaction in which a nitrogen monoxide group is attached to the thiol side chain of the cysteine residue(s) of a protein. Cdk5 S-nitrosylation occurs at Cys83, which is one of the critical amino acids within the ATP-binding pocket of the kinase. Upon S-nitrosylation, Cdk5 exhibits reduced kinase activity, whereas the mutation of Cys83 to alanine on Cdk5 renders the kinase refractory to such inhibition. Meanwhile, p35 S-nitrosylation occurs at Cys92; this modification promotes its proteasome-dependent degradation, consequently resulting in reduced Cdk5 activity. Importantly, S-nitrosylated Cdk5 and p35 can be detected in vivo. While the S-nitrosylation of Cdk5 and p35 was detected in wild-type mouse brain lysate, this specific S-nitrosylation was absent in neuronal nitric oxide synthase-knockout (nNOS) mice. More importantly, Cdk5/p35 S-nitrosylation negatively regulates the activity of Cdk5 in vivo as revealed by enhanced Cdk5 activity in nNOS-knockout mouse brains. Furthermore, Cdk5/p35 S-nitrosylation is implicated in the regulation of neuronal morphogenesis and synaptic plasticity. Blockade of Cdk5 S-nitrosylation in cultured hippocampal neurons enhanced dendritic growth and branching, indicating that Cdk5 S-nitrosylation is a novel mechanism in the regulation of dendritic growth during development. Moreover, Cdk5/p35 S-nitrosylation was found to be involved in the regulation of synaptic function. Cdk5 hyperactivation contributed to synaptic failure upon NO production blockade. Notably, Cdk5/p35 overexpression and silencing phenocopied and reversed these synaptic deficits, respectively, upon pharmacological inhibition or genetic depletion of nNOS. More importantly, blocking p35 S-nitrosylation reduced dendritic spine density and the percentage of mature spines in cultured hippocampal neurons as well as the surface expression of GluA1 in 293T cells. This suggests that p35 S-nitrosylation is critical for the regulation of synaptic function. The present rules collectively demonstrate a novel mechanism in the regulation of the multi-faceted kinase Cdk5 in many neuronal functions including dendritic morphogenesis and synaptic plasticity.

Subjects/Keywords: Cyclin-dependent kinases ; Protein kinases ; Neurotransmitters ; Morphogenesis

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APA (6^th Edition):

Zhang, P. (2013). S-nitrosylation of cyclin-dependent kinase 5 and its activator p35 in neuronal morphogenesis and synaptic function. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-86315 ; https://doi.org/10.14711/thesis-b1266266 ; http://repository.ust.hk/ir/bitstream/1783.1-86315/1/th_redirect.html

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):

Zhang, Peng. “S-nitrosylation of cyclin-dependent kinase 5 and its activator p35 in neuronal morphogenesis and synaptic function.” 2013. Thesis, Hong Kong University of Science and Technology. Accessed April 19, 2021. http://repository.ust.hk/ir/Record/1783.1-86315 ; https://doi.org/10.14711/thesis-b1266266 ; http://repository.ust.hk/ir/bitstream/1783.1-86315/1/th_redirect.html.

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

MLA Handbook (7^th Edition):

Zhang, Peng. “S-nitrosylation of cyclin-dependent kinase 5 and its activator p35 in neuronal morphogenesis and synaptic function.” 2013. Web. 19 Apr 2021.

Vancouver:

Zhang P. S-nitrosylation of cyclin-dependent kinase 5 and its activator p35 in neuronal morphogenesis and synaptic function. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2013. [cited 2021 Apr 19]. Available from: http://repository.ust.hk/ir/Record/1783.1-86315 ; https://doi.org/10.14711/thesis-b1266266 ; http://repository.ust.hk/ir/bitstream/1783.1-86315/1/th_redirect.html.

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

Council of Science Editors:

Zhang P. S-nitrosylation of cyclin-dependent kinase 5 and its activator p35 in neuronal morphogenesis and synaptic function. [Thesis]. Hong Kong University of Science and Technology; 2013. Available from: http://repository.ust.hk/ir/Record/1783.1-86315 ; https://doi.org/10.14711/thesis-b1266266 ; http://repository.ust.hk/ir/bitstream/1783.1-86315/1/th_redirect.html

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

Ryerson University

6. Martin, Zechariah. mTor controls lysosome function by modulating the RAB7 GTPASE.

Degree: 2017, Ryerson University

URL: https://digital.library.ryerson.ca/islandora/object/RULA%3A7189

► Mammalian target of rapamycin (mTOR) is a protein kinase that integrates signals including stress and nutrient availability, to modulate the metabolic state of the cell.… (more)

▼ Mammalian target of rapamycin (mTOR) is a protein kinase that integrates signals including stress and nutrient availability, to modulate the metabolic state of the cell. Interestingly, mTOR complex 1 (mTORC1) is specifically found on lysosomes where it regulates lysosome function, trafficking and morphology. However, little is known about how mTOR interfaces with lysosomal regulators, like the Rab7 GTPase, the canonical mediator of lysosome function, including biogenesis and trafficking to lysosomes to control processes such as antigen presentation and cell signaling. Rab7 can exist in two states. GDP-bound Rab7 is inactive but can be converted to GTP-bound Rab7, the catalytically active form of Rab7. Guanine nucleotide exchange factors (GEFs) are responsible for this conversion. Conversely, GTP-hydrolysis activating proteins (GAPs) facilitate Rab7 GTP hydrolysis, resulting in the conversion of GTP to GDP, rendering Rab7 inactive. We hypothesized that mTOR and Rab7 are functionally linked. Here we show that mTOR negatively controls Rab7. mTOR inhibition through the use of torin, EBSS (an amino acid deprived media) and A-769662 (an AMPK activator), increased levels of both total and active Rab7 (Rab7-GTP) on the lysosomal membrane. This was observed through fractionation, fluorescence microscopy and biochemical pull-down assays. This negative regulation is specific to mTOR, acting through TBC1D15, a Rab7 GAP. mTOR inhibition resulted in a significant reduction in levels of TBC1D15 via ubiquitination, which can be restored upon inhibition of the proteasome. Additionally, mTOR inhibition increased lysosomal proteolytic activity, and enhanced trafficking of material toward the lysosome. Our work suggests that under starvation conditions, trafficking to the lysosome is accelerated, re-establishing nutrient homeostasis. This research could provide a novel link between membrane regulation (Rab7) and metabolic stress sensors (mTOR), allowing insight into the pathogenesis of several metabolic diseases, including certain forms of cancer.

Subjects/Keywords: Lysosomes; Rapamycin; Protein kinases

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APA (6^th Edition):

Martin, Z. (2017). mTor controls lysosome function by modulating the RAB7 GTPASE. (Thesis). Ryerson University. Retrieved from https://digital.library.ryerson.ca/islandora/object/RULA%3A7189

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):

Martin, Zechariah. “mTor controls lysosome function by modulating the RAB7 GTPASE.” 2017. Thesis, Ryerson University. Accessed April 19, 2021. https://digital.library.ryerson.ca/islandora/object/RULA%3A7189.

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

MLA Handbook (7^th Edition):

Martin, Zechariah. “mTor controls lysosome function by modulating the RAB7 GTPASE.” 2017. Web. 19 Apr 2021.

Vancouver:

Martin Z. mTor controls lysosome function by modulating the RAB7 GTPASE. [Internet] [Thesis]. Ryerson University; 2017. [cited 2021 Apr 19]. Available from: https://digital.library.ryerson.ca/islandora/object/RULA%3A7189.

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

Council of Science Editors:

Martin Z. mTor controls lysosome function by modulating the RAB7 GTPASE. [Thesis]. Ryerson University; 2017. Available from: https://digital.library.ryerson.ca/islandora/object/RULA%3A7189

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

Hong Kong University of Science and Technology

7. He, Jing. A preliminary study of PICK1's role in mitochondrial function and Parkinson's disease.

Degree: 2011, Hong Kong University of Science and Technology

URL: http://repository.ust.hk/ir/Record/1783.1-62386 ; https://doi.org/10.14711/thesis-b1155680 ; http://repository.ust.hk/ir/bitstream/1783.1-62386/1/th_redirect.html

► Parkinson’s disease (PD) is a prevalent neurodegenerative disorder that is characterized by bradykinesia, rigidity, resting tremor and postural instability. The death of dopaminergic neurons in… (more)

Subjects/Keywords: Protein kinases ; Mitochondria ; Parkinson's disease

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APA (6^th Edition):

He, J. (2011). A preliminary study of PICK1's role in mitochondrial function and Parkinson's disease. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-62386 ; https://doi.org/10.14711/thesis-b1155680 ; http://repository.ust.hk/ir/bitstream/1783.1-62386/1/th_redirect.html

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):

He, Jing. “A preliminary study of PICK1's role in mitochondrial function and Parkinson's disease.” 2011. Thesis, Hong Kong University of Science and Technology. Accessed April 19, 2021. http://repository.ust.hk/ir/Record/1783.1-62386 ; https://doi.org/10.14711/thesis-b1155680 ; http://repository.ust.hk/ir/bitstream/1783.1-62386/1/th_redirect.html.

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

MLA Handbook (7^th Edition):

He, Jing. “A preliminary study of PICK1's role in mitochondrial function and Parkinson's disease.” 2011. Web. 19 Apr 2021.

Vancouver:

He J. A preliminary study of PICK1's role in mitochondrial function and Parkinson's disease. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2011. [cited 2021 Apr 19]. Available from: http://repository.ust.hk/ir/Record/1783.1-62386 ; https://doi.org/10.14711/thesis-b1155680 ; http://repository.ust.hk/ir/bitstream/1783.1-62386/1/th_redirect.html.

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

Council of Science Editors:

He J. A preliminary study of PICK1's role in mitochondrial function and Parkinson's disease. [Thesis]. Hong Kong University of Science and Technology; 2011. Available from: http://repository.ust.hk/ir/Record/1783.1-62386 ; https://doi.org/10.14711/thesis-b1155680 ; http://repository.ust.hk/ir/bitstream/1783.1-62386/1/th_redirect.html

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

Hong Kong University of Science and Technology

8. Tang, Jing. Functional characterization of Cdk5-dependent Mst3 phosphorylation and Mst3 activity in regulating cortical development.

Degree: 2013, Hong Kong University of Science and Technology

URL: http://repository.ust.hk/ir/Record/1783.1-86316 ; https://doi.org/10.14711/thesis-b1266307 ; http://repository.ust.hk/ir/bitstream/1783.1-86316/1/th_redirect.html

► The cerebral cortex is the outermost layered structure of the cerebrum in humans and some other vertebrates. It serves as the organization center of the… (more)

▼ The cerebral cortex is the outermost layered structure of the cerebrum in humans and some other vertebrates. It serves as the organization center of the brain and is involved in memory, attention, thought, language, movement, and emotion. In humans, the cerebral cortex comprises 6 layers, 2 to 4 mm thick and contains between 10 and 14 billion neurons. The radial migration of newborn neurons is critical for cerebral cortex lamination. Proper neuronal migration requires the precise and rapid reorganization of the actin and microtubule cytoskeleton. However, the signaling mechanisms underlying these processes are not well understood. The present study reveals that Mst3, a serine/threonine kinase highly expressed in the developing mouse brain, is essential for neuronal migration and final neuronal positioning in the developing mouse neocortex. Mst3 silencing by in utero electroporation perturbs the multipolar–bipolar transition of migrating neurons and significantly retards radial migration. The dendritic arborization as well as the upper cortical neurons excitability is also impaired in Mst3 knockdown neurons. The kinase activity of Mst3 is essential for its functions in neuronal morphogenesis and migration, and is regulated via Ser79 phosphorylation by a serine/threonine kinase, cyclin-dependent kinase 5 (Cdk5). Interestingly, Mst3 regulates neuronal migration by modulating the activity of RhoA, a Rho GTPase critical for actin cytoskeletal reorganization. The present results show that Mst3 phosphorylates RhoA at Ser26, thereby negatively regulating the GTPase activity of RhoA. Importantly, RhoA knockdown restores normal neuronal migration in Mst3-knockdown cortices. These findings collectively indicate that Cdk5/Mst3 signaling pathway regulates neuronal migration via RhoA-dependent actin dynamics. The convergence of various kinase signaling pathways toward cytoskeletal organization and remodeling during neuronal migration indicates that corticogenesis is precisely regulated by a complex and coordinated signaling system.

Subjects/Keywords: Cerebral cortex ; Protein kinases

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APA (6^th Edition):

Tang, J. (2013). Functional characterization of Cdk5-dependent Mst3 phosphorylation and Mst3 activity in regulating cortical development. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-86316 ; https://doi.org/10.14711/thesis-b1266307 ; http://repository.ust.hk/ir/bitstream/1783.1-86316/1/th_redirect.html

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):

Tang, Jing. “Functional characterization of Cdk5-dependent Mst3 phosphorylation and Mst3 activity in regulating cortical development.” 2013. Thesis, Hong Kong University of Science and Technology. Accessed April 19, 2021. http://repository.ust.hk/ir/Record/1783.1-86316 ; https://doi.org/10.14711/thesis-b1266307 ; http://repository.ust.hk/ir/bitstream/1783.1-86316/1/th_redirect.html.

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

MLA Handbook (7^th Edition):

Tang, Jing. “Functional characterization of Cdk5-dependent Mst3 phosphorylation and Mst3 activity in regulating cortical development.” 2013. Web. 19 Apr 2021.

Vancouver:

Tang J. Functional characterization of Cdk5-dependent Mst3 phosphorylation and Mst3 activity in regulating cortical development. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2013. [cited 2021 Apr 19]. Available from: http://repository.ust.hk/ir/Record/1783.1-86316 ; https://doi.org/10.14711/thesis-b1266307 ; http://repository.ust.hk/ir/bitstream/1783.1-86316/1/th_redirect.html.

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

Council of Science Editors:

Tang J. Functional characterization of Cdk5-dependent Mst3 phosphorylation and Mst3 activity in regulating cortical development. [Thesis]. Hong Kong University of Science and Technology; 2013. Available from: http://repository.ust.hk/ir/Record/1783.1-86316 ; https://doi.org/10.14711/thesis-b1266307 ; http://repository.ust.hk/ir/bitstream/1783.1-86316/1/th_redirect.html

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

Hong Kong University of Science and Technology

9. Sun, Xulun. Identification and functional characterization of NME7-binding proteins.

Degree: 2014, Hong Kong University of Science and Technology

URL: http://repository.ust.hk/ir/Record/1783.1-87471 ; https://doi.org/10.14711/thesis-b1334235 ; http://repository.ust.hk/ir/bitstream/1783.1-87471/1/th_redirect.html

► In proliferating cells, centrosomes organize the microtubule network and this function depends on the γ-tubulin ring complex (γTuRC). While in quiescent cells, the mother centriole… (more)

▼ In proliferating cells, centrosomes organize the microtubule network and this function depends on the γ-tubulin ring complex (γTuRC). While in quiescent cells, the mother centriole of the centrosome organizes the formation of primary cilia, which are microtubule-based organelles present in most vertebrate cells. Cilia are involved in many essential signaling pathways and plays important roles in helping cells sense extracellular environment. The previous study of our laboratory identified that NME7 (non-metastatic cells 7) is a novel γTuRC component, which promotes γTuRC-mediated microtubule nucleation through its kinase action. NME7 is a member of the nucleoside-diphosphate kinase (NDPK) family. nme7 knockout mice exhibit cilia-related defects, including situs inversus and hydrocephalus. Moreover, we found that NME7 localizes to cilia and is essential for ciliary growth. Considering the NME7’s important role in the events such as microtubule nucleation and ciliogenesis, I identify NME7-binding proteins by mass spectrometry, characterize their interactions with NME7, and uncover the function of these interactions. One of the identified proteins has been reported to block primary cilia assembly in proliferating cells. I found that NME7 and the binding partner have interaction with each other, and the binding protein can also be a competitor for the binding of γTuRC to NME7. Interestingly, the protein level of the binding protein significantly decreased in NME7-depleted cells. I further investigated how NME7 knockdown affects the expression of the binding protein. Protein stability analysis showed that NME7 depletion decreases protein stability of the binding protein. Furthermore, depletion of the binding protein or NME7 resulted in cilia formation in proliferating cells. These results suggest that NME7 may block ciliogenesis in proliferating cells by stabilization of the binding protein. In summary, I provided a series of potential NME7-binding partners which might be essential for the regulation and functional study of NME7.

Subjects/Keywords: Microtubules ; Protein kinases ; Ciliata

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APA (6^th Edition):

Sun, X. (2014). Identification and functional characterization of NME7-binding proteins. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-87471 ; https://doi.org/10.14711/thesis-b1334235 ; http://repository.ust.hk/ir/bitstream/1783.1-87471/1/th_redirect.html

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):

Sun, Xulun. “Identification and functional characterization of NME7-binding proteins.” 2014. Thesis, Hong Kong University of Science and Technology. Accessed April 19, 2021. http://repository.ust.hk/ir/Record/1783.1-87471 ; https://doi.org/10.14711/thesis-b1334235 ; http://repository.ust.hk/ir/bitstream/1783.1-87471/1/th_redirect.html.

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

MLA Handbook (7^th Edition):

Sun, Xulun. “Identification and functional characterization of NME7-binding proteins.” 2014. Web. 19 Apr 2021.

Vancouver:

Sun X. Identification and functional characterization of NME7-binding proteins. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2014. [cited 2021 Apr 19]. Available from: http://repository.ust.hk/ir/Record/1783.1-87471 ; https://doi.org/10.14711/thesis-b1334235 ; http://repository.ust.hk/ir/bitstream/1783.1-87471/1/th_redirect.html.

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

Council of Science Editors:

Sun X. Identification and functional characterization of NME7-binding proteins. [Thesis]. Hong Kong University of Science and Technology; 2014. Available from: http://repository.ust.hk/ir/Record/1783.1-87471 ; https://doi.org/10.14711/thesis-b1334235 ; http://repository.ust.hk/ir/bitstream/1783.1-87471/1/th_redirect.html

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

Hong Kong University of Science and Technology

10. Mao, Zhuo. PICK1 and ICA69's roles in insulin granule biogenesis and Zn²⁺ homeostasis.

Degree: 2013, Hong Kong University of Science and Technology

URL: http://repository.ust.hk/ir/Record/1783.1-76070 ; https://doi.org/10.14711/thesis-b1213285 ; http://repository.ust.hk/ir/bitstream/1783.1-76070/1/th_redirect.html

► Diabetes mellitus is a chronic metabolic disease characterized by elevated blood glucose that results from defects in insulin secretion and/or action. Until now, the cellular… (more)

Subjects/Keywords: Protein kinases ; Insulin ; Somatomedin ; Homeostasis

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APA (6^th Edition):

Mao, Z. (2013). PICK1 and ICA69's roles in insulin granule biogenesis and Zn²⁺ homeostasis. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-76070 ; https://doi.org/10.14711/thesis-b1213285 ; http://repository.ust.hk/ir/bitstream/1783.1-76070/1/th_redirect.html

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):

Mao, Zhuo. “PICK1 and ICA69's roles in insulin granule biogenesis and Zn²⁺ homeostasis.” 2013. Thesis, Hong Kong University of Science and Technology. Accessed April 19, 2021. http://repository.ust.hk/ir/Record/1783.1-76070 ; https://doi.org/10.14711/thesis-b1213285 ; http://repository.ust.hk/ir/bitstream/1783.1-76070/1/th_redirect.html.

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

MLA Handbook (7^th Edition):

Mao, Zhuo. “PICK1 and ICA69's roles in insulin granule biogenesis and Zn²⁺ homeostasis.” 2013. Web. 19 Apr 2021.

Vancouver:

Mao Z. PICK1 and ICA69's roles in insulin granule biogenesis and Zn²⁺ homeostasis. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2013. [cited 2021 Apr 19]. Available from: http://repository.ust.hk/ir/Record/1783.1-76070 ; https://doi.org/10.14711/thesis-b1213285 ; http://repository.ust.hk/ir/bitstream/1783.1-76070/1/th_redirect.html.

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

Council of Science Editors:

Mao Z. PICK1 and ICA69's roles in insulin granule biogenesis and Zn²⁺ homeostasis. [Thesis]. Hong Kong University of Science and Technology; 2013. Available from: http://repository.ust.hk/ir/Record/1783.1-76070 ; https://doi.org/10.14711/thesis-b1213285 ; http://repository.ust.hk/ir/bitstream/1783.1-76070/1/th_redirect.html

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

Rutgers University

11. Rane, Chetan K., 1989-. PAK4 as a drug target in breast cancer therapy.

Degree: PhD, Pharmacology, Cellular and Molecular, 2017, Rutgers University

URL: https://rucore.libraries.rutgers.edu/rutgers-lib/54913/

►

PAK4, belonging to Group II PAKs, is an important signaling protein with key roles in regulating cell growth, cell survival and cell morphology. PAK4 protein… (more)

▼

PAK4, belonging to Group II PAKs, is an important signaling protein with key roles in regulating cell growth, cell survival and cell morphology. PAK4 protein levels are higher in several subtypes of breast cancer cells and PAK4 gene is amplified in basal like breast cancer. PAK4 overexpression in a mouse mammary epithelial cell line (iMMEC) results in oncogenic transformation of these cells, while siRNA mediated PAK4 down regulation in a human triple negative breast cancer cell line, MDA-MB-231, resulted in significant inhibition of its tumorigenic potential. These results point to a central role for PAK4 in mammary tumorigenesis. PAK4 expression pattern makes it an attractive drug target, however, it is important to note that PAK4 has both kinase-dependent and – independent functions in regulating tumor formation. Hence, blocking its kinase activity alone is insufficient in blocking its tumorigenic potential. Our lab collaborated with Karyopharm Therapeutics to investigate a novel PAK4 inhibitor, KPT-9274. I observed that treatment with KPT-9274 and KPT-8752 (isoform of KPT-9274) inhibited the cell growth, cell survival and cell motility of breast cancer cell lines, with this effect most significantly observed in triple negative breast cancer cell lines. I observed that treatment with KPT inhibitors inhibited PAK4 protein levels along with PAK4 associated downstream signaling pathways in triple negative breast cancer cell lines. Most importantly, I observed that KPT- 9274 significantly inhibited tumor growth in mouse xenograft models of 3 human triple negative breast cancer cell lines. KPT-9274 was capable of reducing steady state PAK4 protein levels in vivo, without significantly affecting PAK1 protein levels, indicating that KPT-9274 exhibits in vivo PAK4 specificity. This study shows that PAK4 can serve as a novel drug target in triple negative breast cancer therapy and KPT-9274 can have clinical benefits for the triple negative breast cancer population. Next, I analyzed RNA-seq data of samples collected from non-transformed WT iMMECs and iMMECs overexpressing PAK4, that form tumors in mice. Sequencing analysis identified several genes previously unknown to be regulated by PAK4. Using q-PCR, I was able to validate the RNAseq data, further suggesting that RNA-seq is a promising and reproducible tool to study PAK4 induced transcriptional changes. This study reveals the PAK4 transcriptome profile in mammary tumor forming cells, and can provide translational utility in other types of cancers as well. Delineating the varied effectors of PAK4 signaling cascade will help uncover novel biomarkers for cancer, with some serving as potential therapeutic targets.

Advisors/Committee Members: Kong, Tony (chair), Liu, Fang (co-chair), Minden, Audrey (internal member), Cai, Li (outside member), School of Graduate Studies.

Subjects/Keywords: Breast – Cancer – Treatment; Protein kinases

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APA (6^th Edition):

Rane, Chetan K., 1. (2017). PAK4 as a drug target in breast cancer therapy. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/54913/

Chicago Manual of Style (16^th Edition):

Rane, Chetan K., 1989-. “PAK4 as a drug target in breast cancer therapy.” 2017. Doctoral Dissertation, Rutgers University. Accessed April 19, 2021. https://rucore.libraries.rutgers.edu/rutgers-lib/54913/.

MLA Handbook (7^th Edition):

Rane, Chetan K., 1989-. “PAK4 as a drug target in breast cancer therapy.” 2017. Web. 19 Apr 2021.

Vancouver:

Rane, Chetan K. 1. PAK4 as a drug target in breast cancer therapy. [Internet] [Doctoral dissertation]. Rutgers University; 2017. [cited 2021 Apr 19]. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/54913/.

Council of Science Editors:

Rane, Chetan K. 1. PAK4 as a drug target in breast cancer therapy. [Doctoral Dissertation]. Rutgers University; 2017. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/54913/

Macquarie University

12. Hardianto, Ari. Structural bioinformatics studies of fluorinated balanol analogues as protein kinase C inhibitors.

Degree: 2017, Macquarie University

URL: http://hdl.handle.net/1959.14/1280509

►

Theoretical thesis.

Bibliography: pages 220-229.

Chapter 1. Introduction – Chapter 2. Methods and applications – Chapter 3. Divergent response of homologous ATP sites to stereospecific… (more)

▼

Theoretical thesis.

Bibliography: pages 220-229.

Chapter 1. Introduction – Chapter 2. Methods and applications – Chapter 3. Divergent response of homologous ATP sites to stereospecific ligand fluorination for selectivity enhancement – Chapter 4. Exploration of charge states of balanol analogues acting as ATP-competitive inhibitors in kinases – Chapter 5. Molecular dynamics simulations reveal a single amino acid residue important for global fluorine effect in the binding response of protein kinase C ε and cAMP-dependent protein kinase to fluorinated balanol analogues – Chapter 6. Diverse dynamic features of novel protein kinase C (PKC) isozymes determine selectivity of a fluorinated balanol analogue to PKCε – Chapter 7. Conclusions and future directions.

(-)-Balanol, a fungal natural product, is a non-selective inhibitor for protein kinase A (PKA) and protein kinase C (PKC) isozymes, binding to the adenosine triphosphate (ATP) site. Improving selectivity of balanol to a specific kinase is vital because most PKC isozymes can act as tumour promoters or suppressors depending on the cancer type. Designing selective inhibitors is a big challenge due to high conservation of ATP sites among PKC isozymes. Many structure-activity relationship studies on balanol have be en carried out but did not achieve substantial selectivity improvement. More recently, our group successfully performed stereospecific fluorinations on balanol and generated some analogues with an analogue showing improved selectivity for PKCε. This PKC isozyme is consistently implicated in tumorigenesis and a potential target for anticancer drugs. Thus, understanding the origin to this fluorine-based selectivity will be valuable for designing better balanol-based ATP-mimicking inhibitors. The overall objective of this thesis is to gain such understanding using structural b ioinformatics methods. Analysis data and conclusions drawn are documented to facilitate the design of potential novel balanol-based inhibitors. Molecular docking simulations of balanol and fluorinated balanol analogues (referred as balanoids) were carried out to the crystal structure of mouse PKA, which shares high sequence identity with human PKA , and to a homology model of PK Cε. These approaches provided information of static binding modes of balanoids in both kinases. This investigation provides preliminary results to decipher fluorine-based selectivity that stereospecific fluorination has local and remote effect, which is protein-dependent, to control balanol conformation in the homologous ATP sites. Molecular dynamics (MD) simulation approach can provide a deeper understanding of the binding of balanoids to PKA, PKCε, and other PKC isozymes since it allows the investigation of intermolecular interaction dynamics between the ligand and residues at the binding site. At the outset, a comprehensive exploration of the charge states of different balanoids was carried out. This study identified specific charge states of balanoids that correlate well with experiment and…

Advisors/Committee Members: Macquarie University. Department of Chemistry and Biomolecular Science.

Subjects/Keywords: Protein kinases; Fluorination; inhibitors; balanol

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APA (6^th Edition):

Hardianto, A. (2017). Structural bioinformatics studies of fluorinated balanol analogues as protein kinase C inhibitors. (Doctoral Dissertation). Macquarie University. Retrieved from http://hdl.handle.net/1959.14/1280509

Chicago Manual of Style (16^th Edition):

Hardianto, Ari. “Structural bioinformatics studies of fluorinated balanol analogues as protein kinase C inhibitors.” 2017. Doctoral Dissertation, Macquarie University. Accessed April 19, 2021. http://hdl.handle.net/1959.14/1280509.

MLA Handbook (7^th Edition):

Hardianto, Ari. “Structural bioinformatics studies of fluorinated balanol analogues as protein kinase C inhibitors.” 2017. Web. 19 Apr 2021.

Vancouver:

Hardianto A. Structural bioinformatics studies of fluorinated balanol analogues as protein kinase C inhibitors. [Internet] [Doctoral dissertation]. Macquarie University; 2017. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/1959.14/1280509.

Council of Science Editors:

Hardianto A. Structural bioinformatics studies of fluorinated balanol analogues as protein kinase C inhibitors. [Doctoral Dissertation]. Macquarie University; 2017. Available from: http://hdl.handle.net/1959.14/1280509

University of California – San Francisco

13. Won, Angela P. The Role of Protein-Protein Interactions in Shaping MAP Kinase Kinase Identity.

Degree: Biochemistry and Molecular Biology, 2010, University of California – San Francisco

URL: http://www.escholarship.org/uc/item/6st633p1

► Eukaryotic cells process information through discrete signaling pathways that must maintain high signal fidelity to ensure proper response to environmental stimuli. Often, the signaling proteins… (more)

▼ Eukaryotic cells process information through discrete signaling pathways that must maintain high signal fidelity to ensure proper response to environmental stimuli. Often, the signaling proteins in these pathways use shared interaction elements, both catalytic domains and protein-protein interactions. These elements help define network connectivity and guide information flow. Within the yeast Saccharomyces cerevisae, four distinct mitogen activated protein kinase kinases (MAPKKs) share closely related catalytic domains yet act in separate critical pathways. How have these four related kinases diverged to take on four distinct functional roles? Within this thesis, I explore the relative contributions of modular interaction domains and motifs versus catalytic specificity in defining a kinases' identity. We probe kinase identity by asking whether we can use recruitment interactions to force other MAPKK catalytic domains to play the functional role of the mating MAPKK, Ste7. We find that two alternative MAPKK's, the osmoresponse MAPKK Pbs2 and the hypotonic response MAPKK Mkk2, can be forced to functionally replace the mating MAPKK Ste7, but only if the proper ensemble of recruitment interactions are overlaid on their catalytic domains. Further, we find that these alternative kinases do not exhibit cross-pathway activity and are restricted towards one identity. These results indicate recruitment interactions can play a dominant role in defining functional identity within a family, and is consistent with a model in which new kinase functions can arise through recombination of existing catalytic domains with new interaction modules. However, these recruitment interactions cannot be used in a "plug and play" method to alter any kinase's specificity. We find that addition of Ste7 recruitment interactions does not convert the identity of the hypotonic shock MAPKK, Mkk1. Further, subtle differences are observed in the temporal activity and level of flux of the converted alternative kinases. Altogether, these results indicate that although recruitment interactions can be utilized as a powerful tool to alter functional identity, evolution may have always insured pathway fidelity in some instances through the intrinsic contributions of kinase catalytic domains.

Subjects/Keywords: Biology, Molecular; MAP kinases; protein-protein interactions

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APA (6^th Edition):

Won, A. P. (2010). The Role of Protein-Protein Interactions in Shaping MAP Kinase Kinase Identity. (Thesis). University of California – San Francisco. Retrieved from http://www.escholarship.org/uc/item/6st633p1

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):

Won, Angela P. “The Role of Protein-Protein Interactions in Shaping MAP Kinase Kinase Identity.” 2010. Thesis, University of California – San Francisco. Accessed April 19, 2021. http://www.escholarship.org/uc/item/6st633p1.

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

MLA Handbook (7^th Edition):

Won, Angela P. “The Role of Protein-Protein Interactions in Shaping MAP Kinase Kinase Identity.” 2010. Web. 19 Apr 2021.

Vancouver:

Won AP. The Role of Protein-Protein Interactions in Shaping MAP Kinase Kinase Identity. [Internet] [Thesis]. University of California – San Francisco; 2010. [cited 2021 Apr 19]. Available from: http://www.escholarship.org/uc/item/6st633p1.

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

Council of Science Editors:

Won AP. The Role of Protein-Protein Interactions in Shaping MAP Kinase Kinase Identity. [Thesis]. University of California – San Francisco; 2010. Available from: http://www.escholarship.org/uc/item/6st633p1

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

King Abdullah University of Science and Technology

14. Diaz Galicia, Miriam Escarlet. Engineering of kinase-based protein interacting devices: active expression of tyrosine kinase domains.

Degree: Biological and Environmental Sciences and Engineering (BESE) Division, 2018, King Abdullah University of Science and Technology

URL: http://hdl.handle.net/10754/627877

► Protein-protein interactions modulate cellular processes in health and disease. However, tracing weak or rare associations or dissociations of proteins is not a trivial task. Kinases… (more)

Subjects/Keywords: Kinases; Synthetic Biology; Protein-Protein Interaction

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APA (6^th Edition):

Diaz Galicia, M. E. (2018). Engineering of kinase-based protein interacting devices: active expression of tyrosine kinase domains. (Thesis). King Abdullah University of Science and Technology. Retrieved from http://hdl.handle.net/10754/627877

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):

Diaz Galicia, Miriam Escarlet. “Engineering of kinase-based protein interacting devices: active expression of tyrosine kinase domains.” 2018. Thesis, King Abdullah University of Science and Technology. Accessed April 19, 2021. http://hdl.handle.net/10754/627877.

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

MLA Handbook (7^th Edition):

Diaz Galicia, Miriam Escarlet. “Engineering of kinase-based protein interacting devices: active expression of tyrosine kinase domains.” 2018. Web. 19 Apr 2021.

Vancouver:

Diaz Galicia ME. Engineering of kinase-based protein interacting devices: active expression of tyrosine kinase domains. [Internet] [Thesis]. King Abdullah University of Science and Technology; 2018. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/10754/627877.

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

Council of Science Editors:

Diaz Galicia ME. Engineering of kinase-based protein interacting devices: active expression of tyrosine kinase domains. [Thesis]. King Abdullah University of Science and Technology; 2018. Available from: http://hdl.handle.net/10754/627877

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

15. Moon, Thomas Matthew. Autoinhibition and Chloride Sensing in the WNK1 Kinase.

Degree: 2012, University of Texas Southwestern Medical Center

URL: http://hdl.handle.net/2152.5/1001

► Protein kinases control diverse cellular pathways and have are the subject of intensive study regarding how they maintain specificity toward sub- strates. The research presented… (more)

▼ Protein kinases control diverse cellular pathways and have are the subject of intensive study regarding how they maintain specificity toward sub- strates. The research presented here focuses on a 230kDa serine/threonine protein kinase known as WNK1 (with no lysine {k}). The protein was first cloned by Melanie Cobb's laboratory, and its isoforms have been associated with a monogenic form of hypertension as well as with breast and prostate cancer. Recent data have also shown that WNK1 is necessary for maintaining spindle polarity in mitosis and plays a role in post-mitotic abscission. The function of WNK1 is most commonly associated with the regulation of CCCs via the activation of the WNK1 substrates OSR/SPAK. Prior investigation of the system has demonstrated that CCCs are activated by increasing con- centrations of extracellular salt and by intracellular phosphorylation from the OSR/SPAK kinases. Due to it ubiquity in mammalian cell types, a question has arisen as to how the pathway responds to changes in osmolarity. Further, because of the involvement of WNK1 in a diverse set of cellular mechanisms, how is WNK1 activity and substrate specificity controlled? An autoinhibitory domain of WNK1 was characterized by the Cobb Lab regarding its ability to inhibit the kinase in cis and in trans. In this study, we find that the solution structure of the autoinhibitory domain retains a conserved RFXV binding site from the PASK/FRAY homology 2 (PF2) domain present in OSR/SPAK. Titration data shows that incubation with a 5-mer and a 20-mer peptide derived from the WNK1 kinase domain displays extensive chemical shift perturbation as assessed by 1H,15N-HSQC. Expression of this autoinhibitory domain in cis with the WNK1 kinase domain followed by size-exclusion chromatography shows substantial confor- mational changes when dialized from high to low salt. A measurement of the activity of the WNK1 kinase domain in the presence of increasing amounts of sodium chloride indicate an IC50 of 130mM. Further biophysical investigation using differential scanning fluorimetry with the kinase domain shows that the domain undergoes substantial increases in domain stabilization as the concen- tration of salt is increased. Continued analysis of this phenomena has pointed toward evidence of anion sensing by the WNK1 kinase domain. Other protein kinases studied in our lab do not exhibit this salt sensitivity. To determine the binding site of chloride in the WNK1 kinase domain, the inactive WNK1 kinase was cocrystallized in the presence of sodium bro- mide. A dataset was collected using the bromine anomalous edge (0.92 ̊A). The anomalous difference fourier map was calculated and a 5.2 σ peak was observed at the N-terminus of the 3.10 helix present in the DLG motif of the activation loop. To corroborate these data, the structure of the inactive kinase domain previously crystallized in sodium chloride was re-refined. A similar binding site corroborated by a 2mFo − DFc peak of 5.5 σ was observed in subunit A near the N-terminus of the 3.10 helix. When… Advisors/Committee Members: Goldsmith, Elizabeth J..

Subjects/Keywords: Protein-Serine-Threonine Kinases; Crystallography, X-Ray; Protein Kinases Inhibitors

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APA (6^th Edition):

Moon, T. M. (2012). Autoinhibition and Chloride Sensing in the WNK1 Kinase. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/1001

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):

Moon, Thomas Matthew. “Autoinhibition and Chloride Sensing in the WNK1 Kinase.” 2012. Thesis, University of Texas Southwestern Medical Center. Accessed April 19, 2021. http://hdl.handle.net/2152.5/1001.

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

MLA Handbook (7^th Edition):

Moon, Thomas Matthew. “Autoinhibition and Chloride Sensing in the WNK1 Kinase.” 2012. Web. 19 Apr 2021.

Vancouver:

Moon TM. Autoinhibition and Chloride Sensing in the WNK1 Kinase. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2012. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/2152.5/1001.

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

Council of Science Editors:

Moon TM. Autoinhibition and Chloride Sensing in the WNK1 Kinase. [Thesis]. University of Texas Southwestern Medical Center; 2012. Available from: http://hdl.handle.net/2152.5/1001

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

Michigan State University

16. Pizzimenti, Natalie Maria. Mitogen activated protein kinase signaling in mouse skeletal muscle.

Degree: 2014, Michigan State University

URL: http://etd.lib.msu.edu/islandora/object/etd:2416

►

Thesis M.S. Michigan State University. Physiology - Master of Science 2014.

AMP activated protein kinase (AMPK) and p38 mitogen activated protein kinases (MAPKs) are activated… (more)

Subjects/Keywords: Physiology; Mitochondria – Formation; Protein kinases; Mitogen-activated protein kinases

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APA (6^th Edition):

Pizzimenti, N. M. (2014). Mitogen activated protein kinase signaling in mouse skeletal muscle. (Thesis). Michigan State University. Retrieved from http://etd.lib.msu.edu/islandora/object/etd:2416

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):

Pizzimenti, Natalie Maria. “Mitogen activated protein kinase signaling in mouse skeletal muscle.” 2014. Thesis, Michigan State University. Accessed April 19, 2021. http://etd.lib.msu.edu/islandora/object/etd:2416.

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

MLA Handbook (7^th Edition):

Pizzimenti, Natalie Maria. “Mitogen activated protein kinase signaling in mouse skeletal muscle.” 2014. Web. 19 Apr 2021.

Vancouver:

Pizzimenti NM. Mitogen activated protein kinase signaling in mouse skeletal muscle. [Internet] [Thesis]. Michigan State University; 2014. [cited 2021 Apr 19]. Available from: http://etd.lib.msu.edu/islandora/object/etd:2416.

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

Council of Science Editors:

Pizzimenti NM. Mitogen activated protein kinase signaling in mouse skeletal muscle. [Thesis]. Michigan State University; 2014. Available from: http://etd.lib.msu.edu/islandora/object/etd:2416

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

Indian Institute of Science

17. Rakshambikai, R. Structural and Evolutionary Analyses of Signalling Proteins with Special Reference to Protein Kinases.

Degree: PhD, Faculty of Science, 2018, Indian Institute of Science

URL: http://etd.iisc.ac.in/handle/2005/3188

► Cellular response to environmental changes involves a wide repertoire of complex signalling systems often resulting in up and down regulation of various genes. These mechanisms… (more)

Subjects/Keywords: Cellular Signal Transduction; Kinase Network; Protein Kinases; Signalling Proteins; Protein Signalling; Protein Kinase Phosphorylates; Rogue Kinases; Hybrid Kinases; Takifugu Kinases; Zebrafish Kinases; PIM Kinases; Takifugu Rubripes; Rogue Kinase; Molecular Biophysics

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APA (6^th Edition):

Rakshambikai, R. (2018). Structural and Evolutionary Analyses of Signalling Proteins with Special Reference to Protein Kinases. (Doctoral Dissertation). Indian Institute of Science. Retrieved from http://etd.iisc.ac.in/handle/2005/3188

Chicago Manual of Style (16^th Edition):

Rakshambikai, R. “Structural and Evolutionary Analyses of Signalling Proteins with Special Reference to Protein Kinases.” 2018. Doctoral Dissertation, Indian Institute of Science. Accessed April 19, 2021. http://etd.iisc.ac.in/handle/2005/3188.

MLA Handbook (7^th Edition):

Rakshambikai, R. “Structural and Evolutionary Analyses of Signalling Proteins with Special Reference to Protein Kinases.” 2018. Web. 19 Apr 2021.

Vancouver:

Rakshambikai R. Structural and Evolutionary Analyses of Signalling Proteins with Special Reference to Protein Kinases. [Internet] [Doctoral dissertation]. Indian Institute of Science; 2018. [cited 2021 Apr 19]. Available from: http://etd.iisc.ac.in/handle/2005/3188.

Council of Science Editors:

Rakshambikai R. Structural and Evolutionary Analyses of Signalling Proteins with Special Reference to Protein Kinases. [Doctoral Dissertation]. Indian Institute of Science; 2018. Available from: http://etd.iisc.ac.in/handle/2005/3188

Hong Kong University of Science and Technology

18. Wang, Chihao. Biochemical and structural characterization of interactions within par complex.

Degree: 2012, Hong Kong University of Science and Technology

URL: http://repository.ust.hk/ir/Record/1783.1-7817 ; https://doi.org/10.14711/thesis-b1207876 ; http://repository.ust.hk/ir/bitstream/1783.1-7817/1/th_redirect.html

► Cell polarity refers to asymmetric organization of cell structure and differential distribution of cellular materials. It is implicated in a variety of processes including early… (more)

▼ Cell polarity refers to asymmetric organization of cell structure and differential distribution of cellular materials. It is implicated in a variety of processes including early patterning of organisms, development of organs, stem cell self-renew, junction formation in epithelial cells, cell migration and axonal specification in neurons. In multicellular organisms, the Par complex which is composed of scaffold proteins PAR3 and PAR6 (PARtitioning-defective 3 and 6) and the serine/threonine protein kinase aPKC (atypical Protein Kinase C) is involved in all known cell polarity events. This protein complex is thought to receive upstream polarization signals, amplify and relay them downstream to induce cellular responses including cytoskeleton rearrangements and protein localization changes. aPKC is the only enzyme in the Par complex, thus it is a good candidate to amplify polarity signals and to transduce them to downstream. However, neither the substrate specificity nor the regulation mechanism is clear for the enzyme. The catalytic domain of aPKC has been reported to bind to and phosphorylate the aPKC binding domain of PAR3. To study these questions, biochemical studies were carried out to map the minimal aPKC binding region of PAR3 and to identify the phosphorylation site(s) of the kinase. The complex structure of aPKC catalytic domain-PAR3 peptide was solved by X-ray crystallography. The structure, together with biochemistry studies, reveals a set of substrate recognition sites within the aPKC catalytic domain, and allows the consensus substrate sequence of aPKC to be discerned. An unexpected finding from the structure of the aPKC catalytic domain-PAR3 peptide complex was that the kinase domain assumes an active conformation without the activation loop phosphorylation. This finding suggests that the activity regulation of aPKC originates from a region(s) outside the kinase’s catalytic domain. I further found that the pseudosubstrate sequence of aPKC can directly regulate the kinase activity by inhibiting substrate from binding.

Subjects/Keywords: Protein-protein interactions ; Protein kinase C ; Protein kinases

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APA (6^th Edition):

Wang, C. (2012). Biochemical and structural characterization of interactions within par complex. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-7817 ; https://doi.org/10.14711/thesis-b1207876 ; http://repository.ust.hk/ir/bitstream/1783.1-7817/1/th_redirect.html

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):

Wang, Chihao. “Biochemical and structural characterization of interactions within par complex.” 2012. Thesis, Hong Kong University of Science and Technology. Accessed April 19, 2021. http://repository.ust.hk/ir/Record/1783.1-7817 ; https://doi.org/10.14711/thesis-b1207876 ; http://repository.ust.hk/ir/bitstream/1783.1-7817/1/th_redirect.html.

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

MLA Handbook (7^th Edition):

Wang, Chihao. “Biochemical and structural characterization of interactions within par complex.” 2012. Web. 19 Apr 2021.

Vancouver:

Wang C. Biochemical and structural characterization of interactions within par complex. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2012. [cited 2021 Apr 19]. Available from: http://repository.ust.hk/ir/Record/1783.1-7817 ; https://doi.org/10.14711/thesis-b1207876 ; http://repository.ust.hk/ir/bitstream/1783.1-7817/1/th_redirect.html.

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

Council of Science Editors:

Wang C. Biochemical and structural characterization of interactions within par complex. [Thesis]. Hong Kong University of Science and Technology; 2012. Available from: http://repository.ust.hk/ir/Record/1783.1-7817 ; https://doi.org/10.14711/thesis-b1207876 ; http://repository.ust.hk/ir/bitstream/1783.1-7817/1/th_redirect.html

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

19. Zaman, Aubhishek. Dynamic Modulation of Exocyst Interaction Networks Integrates Hippo and mTOR Pathway Response to Pathogen Detection.

Degree: 2017, University of Texas Southwestern Medical Center

URL: http://hdl.handle.net/2152.5/7737

► Monomeric RALGTPases, via direct binding to the exocyst (a.k.a Sec6/8 complex), help mount productive cell autonomous responses to trophic and immunogenic signals. However, RAL-exocyst downstream… (more)

Subjects/Keywords: Protein-Serine-Threonine Kinases; Signal Transduction; TOR Serine-Threonine Kinases

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APA (6^th Edition):

Zaman, A. (2017). Dynamic Modulation of Exocyst Interaction Networks Integrates Hippo and mTOR Pathway Response to Pathogen Detection. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/7737

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):

Zaman, Aubhishek. “Dynamic Modulation of Exocyst Interaction Networks Integrates Hippo and mTOR Pathway Response to Pathogen Detection.” 2017. Thesis, University of Texas Southwestern Medical Center. Accessed April 19, 2021. http://hdl.handle.net/2152.5/7737.

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

MLA Handbook (7^th Edition):

Zaman, Aubhishek. “Dynamic Modulation of Exocyst Interaction Networks Integrates Hippo and mTOR Pathway Response to Pathogen Detection.” 2017. Web. 19 Apr 2021.

Vancouver:

Zaman A. Dynamic Modulation of Exocyst Interaction Networks Integrates Hippo and mTOR Pathway Response to Pathogen Detection. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2017. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/2152.5/7737.

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

Council of Science Editors:

Zaman A. Dynamic Modulation of Exocyst Interaction Networks Integrates Hippo and mTOR Pathway Response to Pathogen Detection. [Thesis]. University of Texas Southwestern Medical Center; 2017. Available from: http://hdl.handle.net/2152.5/7737

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

20. Shang, Libin. Mechanistic Studies of Autophagy Initiation in Mammalian Cells.

Degree: 2011, University of Texas Southwestern Medical Center

URL: http://hdl.handle.net/2152.5/886

► Macroautophagy (herein referred to as autophagy) is an evolutionarily conserved self-digestive process cells use to adapt to starvation and other stresses. During autophagy, portions of… (more)

Subjects/Keywords: TOR-Serine-Threonine Kinases; Protein-Serine-Threonine Kinases; Autophagy

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APA (6^th Edition):

Shang, L. (2011). Mechanistic Studies of Autophagy Initiation in Mammalian Cells. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/886

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):

Shang, Libin. “Mechanistic Studies of Autophagy Initiation in Mammalian Cells.” 2011. Thesis, University of Texas Southwestern Medical Center. Accessed April 19, 2021. http://hdl.handle.net/2152.5/886.

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

MLA Handbook (7^th Edition):

Shang, Libin. “Mechanistic Studies of Autophagy Initiation in Mammalian Cells.” 2011. Web. 19 Apr 2021.

Vancouver:

Shang L. Mechanistic Studies of Autophagy Initiation in Mammalian Cells. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2011. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/2152.5/886.

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

Council of Science Editors:

Shang L. Mechanistic Studies of Autophagy Initiation in Mammalian Cells. [Thesis]. University of Texas Southwestern Medical Center; 2011. Available from: http://hdl.handle.net/2152.5/886

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

Hong Kong University of Science and Technology

21. Cheng, Kai. Identification of Pctaire1 as a p35-interacting protein and a novel substrate for Cdk5.

Degree: 2003, Hong Kong University of Science and Technology

URL: http://repository.ust.hk/ir/Record/1783.1-1318 ; https://doi.org/10.14711/thesis-b802008 ; http://repository.ust.hk/ir/bitstream/1783.1-1318/1/th_redirect.html

► Cyclin-dependent kinase 5 (Cdk5) is a member of Cdk family. While other members of Cdk family associate with cyclins, Cdk5 interacts with its neuronal specific… (more)

Subjects/Keywords: Cyclin-dependent kinases ; Protein kinases

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APA (6^th Edition):

Cheng, K. (2003). Identification of Pctaire1 as a p35-interacting protein and a novel substrate for Cdk5. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-1318 ; https://doi.org/10.14711/thesis-b802008 ; http://repository.ust.hk/ir/bitstream/1783.1-1318/1/th_redirect.html

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):

Cheng, Kai. “Identification of Pctaire1 as a p35-interacting protein and a novel substrate for Cdk5.” 2003. Thesis, Hong Kong University of Science and Technology. Accessed April 19, 2021. http://repository.ust.hk/ir/Record/1783.1-1318 ; https://doi.org/10.14711/thesis-b802008 ; http://repository.ust.hk/ir/bitstream/1783.1-1318/1/th_redirect.html.

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

MLA Handbook (7^th Edition):

Cheng, Kai. “Identification of Pctaire1 as a p35-interacting protein and a novel substrate for Cdk5.” 2003. Web. 19 Apr 2021.

Vancouver:

Cheng K. Identification of Pctaire1 as a p35-interacting protein and a novel substrate for Cdk5. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2003. [cited 2021 Apr 19]. Available from: http://repository.ust.hk/ir/Record/1783.1-1318 ; https://doi.org/10.14711/thesis-b802008 ; http://repository.ust.hk/ir/bitstream/1783.1-1318/1/th_redirect.html.

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

Council of Science Editors:

Cheng K. Identification of Pctaire1 as a p35-interacting protein and a novel substrate for Cdk5. [Thesis]. Hong Kong University of Science and Technology; 2003. Available from: http://repository.ust.hk/ir/Record/1783.1-1318 ; https://doi.org/10.14711/thesis-b802008 ; http://repository.ust.hk/ir/bitstream/1783.1-1318/1/th_redirect.html

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

Hong Kong University of Science and Technology

22. Cheung, Anthony Yik-Hang. Identification and characterization of endophilin B1 as a p35 interacting protein and a Cdk5 substrate.

Degree: 2007, Hong Kong University of Science and Technology

URL: http://repository.ust.hk/ir/Record/1783.1-3783 ; https://doi.org/10.14711/thesis-b986932 ; http://repository.ust.hk/ir/bitstream/1783.1-3783/1/th_redirect.html

► Cyclin-dependent kinase 5 (Cdk5) is a unique member of the Cdk family that has been shown to play a diverse role in neural development. In… (more)

▼ Cyclin-dependent kinase 5 (Cdk5) is a unique member of the Cdk family that has been shown to play a diverse role in neural development. In the current study, we have demonstrated that p35, the activator of cyclin-dependent kinase 5 (Cdk5), associates with endophilin B1 (EndoB1) both in vitro and in vivo. Furthermore, we found that active Cdk5 phosphorylates EndoB1 in vitro, as well as in the EndoB1-overexpressing mammalian cells at Thr-145 of EndoB1. To examine the functional significance of this phosphorylation, we sought to examine how Cdk5 activity modulates the putative function of EndoB1. EndoB1 has been reported to bind to lipids, tubulate liposomes, in addition to exhibiting lysophosphatidic acid acyltransferase activity. Unlike endophilin A1, which interacts with endocytic proteins such as amphiphysin and dynamin to regulate endocytosis of synaptic vesicles, recent studies suggest that EndoB1 may be involved in intracellular protein trafficking and maintenance of mitochondria morphology. We observed that EndoB1 co-localizes with EEA1-positive vesicles in mammalian cells, suggesting that EndoB1 may function at early endosome and is involved in the regulation of the endolysosomal pathway. Using PC12 cells as a model, we investigated if EndoB1 may affect neurite outgrowth through modulating trafficking of internalized NGF receptors. We found that knock-down of EndoB1 in PC12 cells markedly inhibited the neurite outgrowth in NGF-treated PC12 cells, indicating that EndoB1 is required for NGF-induced neurite outgrowth. In addition, attenuation of neurite outgrowth was also observed in PC12 cells overexpressing EndoB1 phosphorylation mutant, suggesting that phosphorylation of EndoB1 by Cdk5 was required for neurite outgrowth in PC12 cells. Our findings indicate that phosphorylation of EndoB1 at Thr-T145 is essential for the function of EndoB1, and provide insights into understanding the role of Cdk5/p35 in intracellular trafficking pathways in neuronal development.

Subjects/Keywords: Cyclin-dependent kinases ; Protein kinases

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APA (6^th Edition):

Cheung, A. Y. (2007). Identification and characterization of endophilin B1 as a p35 interacting protein and a Cdk5 substrate. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-3783 ; https://doi.org/10.14711/thesis-b986932 ; http://repository.ust.hk/ir/bitstream/1783.1-3783/1/th_redirect.html

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):

Cheung, Anthony Yik-Hang. “Identification and characterization of endophilin B1 as a p35 interacting protein and a Cdk5 substrate.” 2007. Thesis, Hong Kong University of Science and Technology. Accessed April 19, 2021. http://repository.ust.hk/ir/Record/1783.1-3783 ; https://doi.org/10.14711/thesis-b986932 ; http://repository.ust.hk/ir/bitstream/1783.1-3783/1/th_redirect.html.

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

MLA Handbook (7^th Edition):

Cheung, Anthony Yik-Hang. “Identification and characterization of endophilin B1 as a p35 interacting protein and a Cdk5 substrate.” 2007. Web. 19 Apr 2021.

Vancouver:

Cheung AY. Identification and characterization of endophilin B1 as a p35 interacting protein and a Cdk5 substrate. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2007. [cited 2021 Apr 19]. Available from: http://repository.ust.hk/ir/Record/1783.1-3783 ; https://doi.org/10.14711/thesis-b986932 ; http://repository.ust.hk/ir/bitstream/1783.1-3783/1/th_redirect.html.

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

Council of Science Editors:

Cheung AY. Identification and characterization of endophilin B1 as a p35 interacting protein and a Cdk5 substrate. [Thesis]. Hong Kong University of Science and Technology; 2007. Available from: http://repository.ust.hk/ir/Record/1783.1-3783 ; https://doi.org/10.14711/thesis-b986932 ; http://repository.ust.hk/ir/bitstream/1783.1-3783/1/th_redirect.html

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

Hong Kong University of Science and Technology

23. Wong, Siu Lun. Functional characterization of Cdk5-mediated phosphorylation of endophilin B1 in macroautophagy in models of parkinson's disease.

Degree: 2011, Hong Kong University of Science and Technology

URL: http://repository.ust.hk/ir/Record/1783.1-7348 ; https://doi.org/10.14711/thesis-b1155463 ; http://repository.ust.hk/ir/bitstream/1783.1-7348/1/th_redirect.html

► Macroautophagy is a cellular process that sequesters cytoplasmic content into autophagosomes for subsequent degradation. Precise regulation of macroautophagy ensures cell survival, with either excessive or… (more)

Subjects/Keywords: Cyclin-dependent kinases ; Protein kinases ; Autophagic vacuoles ; Parkinson's disease

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APA (6^th Edition):

Wong, S. L. (2011). Functional characterization of Cdk5-mediated phosphorylation of endophilin B1 in macroautophagy in models of parkinson's disease. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-7348 ; https://doi.org/10.14711/thesis-b1155463 ; http://repository.ust.hk/ir/bitstream/1783.1-7348/1/th_redirect.html

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):

Wong, Siu Lun. “Functional characterization of Cdk5-mediated phosphorylation of endophilin B1 in macroautophagy in models of parkinson's disease.” 2011. Thesis, Hong Kong University of Science and Technology. Accessed April 19, 2021. http://repository.ust.hk/ir/Record/1783.1-7348 ; https://doi.org/10.14711/thesis-b1155463 ; http://repository.ust.hk/ir/bitstream/1783.1-7348/1/th_redirect.html.

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

MLA Handbook (7^th Edition):

Wong, Siu Lun. “Functional characterization of Cdk5-mediated phosphorylation of endophilin B1 in macroautophagy in models of parkinson's disease.” 2011. Web. 19 Apr 2021.

Vancouver:

Wong SL. Functional characterization of Cdk5-mediated phosphorylation of endophilin B1 in macroautophagy in models of parkinson's disease. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2011. [cited 2021 Apr 19]. Available from: http://repository.ust.hk/ir/Record/1783.1-7348 ; https://doi.org/10.14711/thesis-b1155463 ; http://repository.ust.hk/ir/bitstream/1783.1-7348/1/th_redirect.html.

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

Council of Science Editors:

Wong SL. Functional characterization of Cdk5-mediated phosphorylation of endophilin B1 in macroautophagy in models of parkinson's disease. [Thesis]. Hong Kong University of Science and Technology; 2011. Available from: http://repository.ust.hk/ir/Record/1783.1-7348 ; https://doi.org/10.14711/thesis-b1155463 ; http://repository.ust.hk/ir/bitstream/1783.1-7348/1/th_redirect.html

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

Hong Kong University of Science and Technology

24. Ye, Tao. Functional characterization of Cdk5-mediated phosphorylation of RapGEF2 in cortical development.

Degree: 2013, Hong Kong University of Science and Technology

URL: http://repository.ust.hk/ir/Record/1783.1-83612 ; https://doi.org/10.14711/thesis-b1274518 ; http://repository.ust.hk/ir/bitstream/1783.1-83612/1/th_redirect.html

► The functional wiring of the cerebral cortex requires multiple coordinated steps of neuronal migration; the perturbation of which leads to brain malformation and various neuropsychiatric… (more)

Subjects/Keywords: Cerebral cortex ; Growth ; Cellular signal transduction ; Cyclin-dependent kinases ; Protein kinases

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APA (6^th Edition):

Ye, T. (2013). Functional characterization of Cdk5-mediated phosphorylation of RapGEF2 in cortical development. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-83612 ; https://doi.org/10.14711/thesis-b1274518 ; http://repository.ust.hk/ir/bitstream/1783.1-83612/1/th_redirect.html

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):

Ye, Tao. “Functional characterization of Cdk5-mediated phosphorylation of RapGEF2 in cortical development.” 2013. Thesis, Hong Kong University of Science and Technology. Accessed April 19, 2021. http://repository.ust.hk/ir/Record/1783.1-83612 ; https://doi.org/10.14711/thesis-b1274518 ; http://repository.ust.hk/ir/bitstream/1783.1-83612/1/th_redirect.html.

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

MLA Handbook (7^th Edition):

Ye, Tao. “Functional characterization of Cdk5-mediated phosphorylation of RapGEF2 in cortical development.” 2013. Web. 19 Apr 2021.

Vancouver:

Ye T. Functional characterization of Cdk5-mediated phosphorylation of RapGEF2 in cortical development. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2013. [cited 2021 Apr 19]. Available from: http://repository.ust.hk/ir/Record/1783.1-83612 ; https://doi.org/10.14711/thesis-b1274518 ; http://repository.ust.hk/ir/bitstream/1783.1-83612/1/th_redirect.html.

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

Council of Science Editors:

Ye T. Functional characterization of Cdk5-mediated phosphorylation of RapGEF2 in cortical development. [Thesis]. Hong Kong University of Science and Technology; 2013. Available from: http://repository.ust.hk/ir/Record/1783.1-83612 ; https://doi.org/10.14711/thesis-b1274518 ; http://repository.ust.hk/ir/bitstream/1783.1-83612/1/th_redirect.html

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

Hong Kong University of Science and Technology

25. He, Ying. The role of Cdk5 in endophilinB1-mediated regulation of NGF/TrkA trafficking.

Degree: 2011, Hong Kong University of Science and Technology

URL: http://repository.ust.hk/ir/Record/1783.1-7415 ; https://doi.org/10.14711/thesis-b1155478 ; http://repository.ust.hk/ir/bitstream/1783.1-7415/1/th_redirect.html

► Tropomyosin-related kinase A (TrkA) is the cognate receptor for the prototypic neurotrophin nerve growth factor (NGF), which is a well-known member of the neurotrophin family.… (more)

▼ Tropomyosin-related kinase A (TrkA) is the cognate receptor for the prototypic neurotrophin nerve growth factor (NGF), which is a well-known member of the neurotrophin family. Binding of NGF to TrkA receptors induces internalization and trafficking of NGF/TrkA complex through the endocytic pathway. Previous study in our lab found a novel role of endophilin B1, which belongs to a family of lipid binding proteins that mediates generation of high curvature membranes. It is reported that knock-down of endophilin B1 triggers precocious targeting of NGF/TrkA to late endosomes and lysosomes. This leads to marked reduction in TrkA level and attenuation of NGF-induced gene transcription and neurite outgrowth. Recently, our lab has also demonstrated endophilin B1 as a Cdk5 substrate and it is phosphorylated by Cdk5 at Thr145. However, whether Cdk5 may affect NGF/TrkA trafficking through phosphorylation of endophilin B1, thereby regulating NGF-mediated downstream functions, is still an enigma. In this study, we established a cell-based system using streptavidin-fluor568 conjugated dye to label biotinylated TrkA in AP-TrkA overexpressing primary cultured cortical neurons, to examine TrkA trafficking induced by NGF treatment. We further examined the importance of Cdk5 in the regulation of TrkA trafficking by endophilin B1. Cdk5 activity was reduced by treatment with Cdk5 inhibitor roscovitine or RNA interference in cultured cortical neurons. Both roscovitine treatment and knock-down of Cdk5 affected trafficking of TrkA, possibly by blocking receptor internalization or enhancing the early sorting of receptors from early endosome to recycling endosome. We then examined the significance of Thr145 phosphorylation of endophilin B1 on the trafficking of TrkA. We found that phosphorylation of endophilin B1 by Cdk5 at Thr145 may not be implicated in the regulation of TrkA trafficking by Cdk5. These observations suggest that while Cdk5 activity may have an impact on the regulation of NGF/TrkA trafficking, its effect is possibly independent from its phosphorylation of endophilin B1. Our data call for further investigations to delineate the precise mechanisms implicated.

Subjects/Keywords: Cyclin-dependent kinases ; Protein kinases ; Tropomyosins ; Nerve growth factor

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APA (6^th Edition):

He, Y. (2011). The role of Cdk5 in endophilinB1-mediated regulation of NGF/TrkA trafficking. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-7415 ; https://doi.org/10.14711/thesis-b1155478 ; http://repository.ust.hk/ir/bitstream/1783.1-7415/1/th_redirect.html

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):

He, Ying. “The role of Cdk5 in endophilinB1-mediated regulation of NGF/TrkA trafficking.” 2011. Thesis, Hong Kong University of Science and Technology. Accessed April 19, 2021. http://repository.ust.hk/ir/Record/1783.1-7415 ; https://doi.org/10.14711/thesis-b1155478 ; http://repository.ust.hk/ir/bitstream/1783.1-7415/1/th_redirect.html.

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

MLA Handbook (7^th Edition):

He, Ying. “The role of Cdk5 in endophilinB1-mediated regulation of NGF/TrkA trafficking.” 2011. Web. 19 Apr 2021.

Vancouver:

He Y. The role of Cdk5 in endophilinB1-mediated regulation of NGF/TrkA trafficking. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2011. [cited 2021 Apr 19]. Available from: http://repository.ust.hk/ir/Record/1783.1-7415 ; https://doi.org/10.14711/thesis-b1155478 ; http://repository.ust.hk/ir/bitstream/1783.1-7415/1/th_redirect.html.

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

Council of Science Editors:

He Y. The role of Cdk5 in endophilinB1-mediated regulation of NGF/TrkA trafficking. [Thesis]. Hong Kong University of Science and Technology; 2011. Available from: http://repository.ust.hk/ir/Record/1783.1-7415 ; https://doi.org/10.14711/thesis-b1155478 ; http://repository.ust.hk/ir/bitstream/1783.1-7415/1/th_redirect.html

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

Ryerson University

26. Ho, Shannon Cheuk Ying. Characterization of the Regulation and Function of Phosphatidylinositol 3,5-Bisphosphate.

Degree: 2016, Ryerson University

URL: https://digital.library.ryerson.ca/islandora/object/RULA%3A5746

► PtdIns(3,5)P2 is a low abundance phosphoinositide that is involved in a variety of cellular processes. Most notably, PtdIns(3,5)P2 is known to regulate vacuolar/lysosomal morphology. Deficiency… (more)

Subjects/Keywords: Quinacrine; Phosphoinositides – Physiological effect; Protein kinases; Lysosomes

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

APA (6^th Edition):

Ho, S. C. Y. (2016). Characterization of the Regulation and Function of Phosphatidylinositol 3,5-Bisphosphate. (Thesis). Ryerson University. Retrieved from https://digital.library.ryerson.ca/islandora/object/RULA%3A5746

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):

Ho, Shannon Cheuk Ying. “Characterization of the Regulation and Function of Phosphatidylinositol 3,5-Bisphosphate.” 2016. Thesis, Ryerson University. Accessed April 19, 2021. https://digital.library.ryerson.ca/islandora/object/RULA%3A5746.

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

MLA Handbook (7^th Edition):

Ho, Shannon Cheuk Ying. “Characterization of the Regulation and Function of Phosphatidylinositol 3,5-Bisphosphate.” 2016. Web. 19 Apr 2021.

Vancouver:

Ho SCY. Characterization of the Regulation and Function of Phosphatidylinositol 3,5-Bisphosphate. [Internet] [Thesis]. Ryerson University; 2016. [cited 2021 Apr 19]. Available from: https://digital.library.ryerson.ca/islandora/object/RULA%3A5746.

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

Council of Science Editors:

Ho SCY. Characterization of the Regulation and Function of Phosphatidylinositol 3,5-Bisphosphate. [Thesis]. Ryerson University; 2016. Available from: https://digital.library.ryerson.ca/islandora/object/RULA%3A5746

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

University of Tasmania

27. Cleland, Perry J F. Contraction-induced glucose transport into skeletal muscle : the involvement of protein kinase C.

Degree: 1990, University of Tasmania

URL: https://eprints.utas.edu.au/18971/1/whole_ClelandPerryJF1990_thesis.pdf

► The role of PKc as a possible intracellular mediator of exercise-induced increase in skeletal muscle glucose transport was investigated. Two skeletal systems were used, the… (more)

▼ The role of PKc as a possible intracellular mediator of exercise-induced increase in skeletal muscle glucose transport was investigated. Two skeletal systems were used, the in vivo rat gastrocnemius-plantaris-soleus muscle preparation, and the in vitro isolated soleus muscle preparation. PKc was partially purified from gastrocnemius-plantarissoleus skeletal muscle preparations by DE52 anion exchange chromatography. The skeletal muscle content of PKc was found to be higher than previously reported. Levels of PKc activity were found to be comparable to those of published PKa values, which suggest an equally important function for PKc in cellular events. The complete extraction of PKc from skeletal muscle membranes required a high concentration of Triton X100. This suggested that the hydrophobic domain of the enzyme was tightly bound to the membrane bilayer. Analysis of the intracellular distribution showed that a large proportion of the enzyme activity (60%) was associated with the membrane component of resting muscle. Electrical-induced contraction of the gastrocnemius‘ - plantaris-soleus muscle group resulted in a time-dependent translocation of PKc and a 2-fold increase in the concentration of both diacylglycerol and phosphatidic acid. The maximal values for the latter were reached at 2 min and preceded the maximum translocation of PKc (10 min). No PKm formation was detected by the production of a Ca 2+ -, phospholipid-independent histone kinase activity. No reversal of translocated PKc or decrease in the concentrations of diacyglycerol and phosphatidic acid occurred after 30 min of rest following a 5 min period of stimulation in vivo. The translocation of PKc was not influenced by variations in applied load at maximal fiber recruitment, but was dependent on the frequency of non-tetanic stimuli reaching a maximum at 4 Hz. Thus, it is concluded that electrical-induced muscle contraction increased the production of diacylglycerol and the translocation of PKc. This is indictative of enzyme activation. The relationship between PKc and glucose transport was explored, in vivo, by varying the number of tetanic stimuli. Only one train of stimuli (200 ms, 100 Hz) was required for maximum translocation of PKc and for diacylglycerol and phosphatidic acid production. However, more than 35 trains of stimuli were required to activate glucose transport. The electrical stimulation of isolated soleus muscle in vitro increased the rate of glucose transport, but this required 20 min to reach maximum. Therefore, the time course for the activation of glucose transport is slower than PKc translocation. Thus, it is concluded that a "causal" relationship between electrical stimulation and the increase in glucose transport involving PKc activation may exist. In an attempt to further clarify a role for PKc in the mechanism of glucose transport activation isolated soleus muscle was depleted ("downregulated") of PKc activity by prolonged TPA treatment. The response to both insulin and…

Subjects/Keywords: Protein kinases; Muscles

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APA (6^th Edition):

Cleland, P. J. F. (1990). Contraction-induced glucose transport into skeletal muscle : the involvement of protein kinase C. (Thesis). University of Tasmania. Retrieved from https://eprints.utas.edu.au/18971/1/whole_ClelandPerryJF1990_thesis.pdf

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):

Cleland, Perry J F. “Contraction-induced glucose transport into skeletal muscle : the involvement of protein kinase C.” 1990. Thesis, University of Tasmania. Accessed April 19, 2021. https://eprints.utas.edu.au/18971/1/whole_ClelandPerryJF1990_thesis.pdf.

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

MLA Handbook (7^th Edition):

Cleland, Perry J F. “Contraction-induced glucose transport into skeletal muscle : the involvement of protein kinase C.” 1990. Web. 19 Apr 2021.

Vancouver:

Cleland PJF. Contraction-induced glucose transport into skeletal muscle : the involvement of protein kinase C. [Internet] [Thesis]. University of Tasmania; 1990. [cited 2021 Apr 19]. Available from: https://eprints.utas.edu.au/18971/1/whole_ClelandPerryJF1990_thesis.pdf.

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

Council of Science Editors:

Cleland PJF. Contraction-induced glucose transport into skeletal muscle : the involvement of protein kinase C. [Thesis]. University of Tasmania; 1990. Available from: https://eprints.utas.edu.au/18971/1/whole_ClelandPerryJF1990_thesis.pdf

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

Stellenbosch University

28. Van der Westhuyzen, Aletta Elizabeth. Synthesis of novel staurosporine analogues as potential kinase inhibitors.

Degree: MSc, Chemistry and Polymer Science, 2015, Stellenbosch University

URL: http://hdl.handle.net/10019.1/96632

►

ENGLISH ABSTRACT: Protein kinases are enzymes that promote phosphorylation – transferring a phosphate group from ATP to a substrate protein. Due to the central involvement… (more)

▼

ENGLISH ABSTRACT: Protein kinases are enzymes that promote phosphorylation – transferring a phosphate group from ATP to a substrate protein. Due to the central involvement of kinases in growth factor signaling, cell cycle control, apoptosis and angiogenesis, they have been linked to cancer development and are attractive drug targets for cancer therapeutics. Staurosporine is a natural, potent kinase inhibitor, initially isolated from the bacterium Streptomyces staurosporeus. It does not serve as a viable therapeutic drug since it exhibits poor selectivity. However, this natural product has been widely used in research and serves as a “structural muse” for the design of protein kinase inhibitors with improved specificity and selectivity. This project involved the synthesis of potential reversible and irreversible kinase inhibitors inspired by the natural product staurosporine. A primary objective was to develop compounds with improved selectivity, while maintaining the potency of staurosporine. The design strategy incorporated a driving portion, resembling the structural features of staurosporine, carrying a specific warhead to form a reversible or irreversible interaction within the kinase domain. This project comprises of two main parts – the design of pyrrolocarbazole structures and the generation of structures based on the “open” form of the indolocarbazoles. The development of the pyrrolocarbazole compounds was motivated by the encouraging results exhibited by 6-(3-hydroxypropyl)pyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione (29), previously synthesized in our group. The major steps involved in the synthesis were the reduction, oxidation, Wittig, Diels-Alder and aromatization reactions. Introducing different warheads, allowed for the generation of unaromatized and aromatized pyrrolocarbazole target compounds having an N-tether hydroxyl, propargyl and nitrile functionality. The synthesis of the “open” form structures utilized click chemistry. The synthetic methodology towards the bisaryl maleimide structures involved a “double click” approach, which presented various challenges. In addition, the synthesis of indolyl maleimide click products also proved to be difficult. Finally, a promising route towards bisamino maleimide compounds led to the development of two target compounds containing the acryloyl and propargyl warhead functionality respectively. Biochemical screening by German collaborators against the wild type, and two mutant forms of the EGFR kinase, was undertaken with the target compounds, utilizing the HTRF KinEASE-TK assay. Overall, only the aromatized pyrrolocarbazole N-two carbon linker hydroxyl target compound exhibited inhibitory activity in the μM range. Finally, a number of optimization measures are described to potentially improve the inhibitory activity of both the pyrrolocarbazole compounds and bisamino maleimides.

AFRIKAANSE OPSOMMING: Proteïn kinase is ensieme wat fosforilasie bevorder – deur ń fosfaat groep van ATP na ń substraat proteïn oor te plaas. As gevolg van die sentrale betrokkenheid…

Advisors/Committee Members: Van Otterlo, Willem, Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science..

Subjects/Keywords: Protein kinases; EGFR; Cancer therapy; UCTD; Phosphorylation

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

APA (6^th Edition):

Van der Westhuyzen, A. E. (2015). Synthesis of novel staurosporine analogues as potential kinase inhibitors. (Masters Thesis). Stellenbosch University. Retrieved from http://hdl.handle.net/10019.1/96632

Chicago Manual of Style (16^th Edition):

Van der Westhuyzen, Aletta Elizabeth. “Synthesis of novel staurosporine analogues as potential kinase inhibitors.” 2015. Masters Thesis, Stellenbosch University. Accessed April 19, 2021. http://hdl.handle.net/10019.1/96632.

MLA Handbook (7^th Edition):

Van der Westhuyzen, Aletta Elizabeth. “Synthesis of novel staurosporine analogues as potential kinase inhibitors.” 2015. Web. 19 Apr 2021.

Vancouver:

Van der Westhuyzen AE. Synthesis of novel staurosporine analogues as potential kinase inhibitors. [Internet] [Masters thesis]. Stellenbosch University; 2015. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/10019.1/96632.

Council of Science Editors:

Van der Westhuyzen AE. Synthesis of novel staurosporine analogues as potential kinase inhibitors. [Masters Thesis]. Stellenbosch University; 2015. Available from: http://hdl.handle.net/10019.1/96632

University of Johannesburg

29. Bothma, Christiaan. Orgaanspesifieke proteienkinase-aktiwiteite in Triticum aestivum L. kultivar Zaragoza, met spesiale verwysing na die helmknopkultuurtegniek.

Degree: 2014, University of Johannesburg

URL: http://hdl.handle.net/10210/9652

►

M.Sc. (Biochemistry)

The culture of plant anther tissue in vitro, is an important tool which could be used, when perfectedr in the conventional breeding of… (more)

Subjects/Keywords: Plant tissue culture - Experiments; Protein kinases - Research

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

APA (6^th Edition):

Bothma, C. (2014). Orgaanspesifieke proteienkinase-aktiwiteite in Triticum aestivum L. kultivar Zaragoza, met spesiale verwysing na die helmknopkultuurtegniek. (Thesis). University of Johannesburg. Retrieved from http://hdl.handle.net/10210/9652

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):

Bothma, Christiaan. “Orgaanspesifieke proteienkinase-aktiwiteite in Triticum aestivum L. kultivar Zaragoza, met spesiale verwysing na die helmknopkultuurtegniek.” 2014. Thesis, University of Johannesburg. Accessed April 19, 2021. http://hdl.handle.net/10210/9652.

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

MLA Handbook (7^th Edition):

Bothma, Christiaan. “Orgaanspesifieke proteienkinase-aktiwiteite in Triticum aestivum L. kultivar Zaragoza, met spesiale verwysing na die helmknopkultuurtegniek.” 2014. Web. 19 Apr 2021.

Vancouver:

Bothma C. Orgaanspesifieke proteienkinase-aktiwiteite in Triticum aestivum L. kultivar Zaragoza, met spesiale verwysing na die helmknopkultuurtegniek. [Internet] [Thesis]. University of Johannesburg; 2014. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/10210/9652.

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

Council of Science Editors:

Bothma C. Orgaanspesifieke proteienkinase-aktiwiteite in Triticum aestivum L. kultivar Zaragoza, met spesiale verwysing na die helmknopkultuurtegniek. [Thesis]. University of Johannesburg; 2014. Available from: http://hdl.handle.net/10210/9652

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

30. Wedin, Kyle Edward. With No Lysine (WNK) Family Proteins and Their Interaction with Downstream Kinases.

Degree: 2011, University of Texas Southwestern Medical Center

URL: http://hdl.handle.net/2152.5/892

► With no lysine (WNK) kinases are a family of protein kinases characterized by unusual kinase domain architecture. These large proteins, divergent outside of a kinase… (more)

Subjects/Keywords: Protein-Serine-Threonine Kinases; Hypertension; Transcription Factors

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

APA (6^th Edition):

Wedin, K. E. (2011). With No Lysine (WNK) Family Proteins and Their Interaction with Downstream Kinases. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/892

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):

Wedin, Kyle Edward. “With No Lysine (WNK) Family Proteins and Their Interaction with Downstream Kinases.” 2011. Thesis, University of Texas Southwestern Medical Center. Accessed April 19, 2021. http://hdl.handle.net/2152.5/892.

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

MLA Handbook (7^th Edition):

Wedin, Kyle Edward. “With No Lysine (WNK) Family Proteins and Their Interaction with Downstream Kinases.” 2011. Web. 19 Apr 2021.

Vancouver:

Wedin KE. With No Lysine (WNK) Family Proteins and Their Interaction with Downstream Kinases. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2011. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/2152.5/892.

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

Council of Science Editors:

Wedin KE. With No Lysine (WNK) Family Proteins and Their Interaction with Downstream Kinases. [Thesis]. University of Texas Southwestern Medical Center; 2011. Available from: http://hdl.handle.net/2152.5/892

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

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Open Access Theses and Dissertations