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Two Distinct Modes Of Signaling By Vascular Endothelial Growth Factor C Guide Blood And Lymphatic Vessel Patterning In Zebrafish: A Dissertation, Jacques A. Villefranc Aug 2011

Two Distinct Modes Of Signaling By Vascular Endothelial Growth Factor C Guide Blood And Lymphatic Vessel Patterning In Zebrafish: A Dissertation, Jacques A. Villefranc

GSBS Dissertations and Theses

Vascular Endothelial Growth Factor Receptor-3 (VEGFR3/Flt4) and its ligand Vegfc are necessary for development of both blood and lymphatic vasculature in vertebrates. In zebrafish, Vegfc/Flt4 signaling is essential for formation of arteries, veins, and lymphatic vessels. Interestingly, Flt4 appears to utilize distinct signaling pathways during the development of each of these vessels. To identify components of this pathway, we performed a transgenic haploid genetic screen in zebrafish that express EGFP under the control of a blood vessel specific promoter. As a result, we indentified a mutant allele of vascular endothelial growth factor c (vegfc), vegfcum18. vegfcum18 ...


Hsp90-Mediated Maturation Of Kinases And Nuclear Steroid Hormone Receptors: A Dissertation, Natalie W. Pursell Apr 2011

Hsp90-Mediated Maturation Of Kinases And Nuclear Steroid Hormone Receptors: A Dissertation, Natalie W. Pursell

GSBS Dissertations and Theses

Among heat shock proteins, Hsp90 is unusual because it is not required for the proper folding of most cellular proteins but rather is disproportionally linked to the activation of signal transduction proteins including over forty kinases and many steroid hormone receptors. Mutated forms of many Hsp90 clients are causative agents in cancer, making Hsp90 a promising pharmacological target. Many small molecular inhibitors have been identified that competitively bind to the ATP binding site of Hsp90, some of which are in clinical trials as anticancer agents. Although the activation of kinase and hormone receptor clients by Hsp90 and its co-chaperones has ...


Converging Pathways In The Regulation Of Longevity And Metabolism In Caenorhabditis Elegans: A Dissertation, Sri Devi Narasimhan Nov 2010

Converging Pathways In The Regulation Of Longevity And Metabolism In Caenorhabditis Elegans: A Dissertation, Sri Devi Narasimhan

GSBS Dissertations and Theses

The lifespan of an organism is determined by a complex array of genetic, environmental and nutritional factors. Yet single gene manipulations have been shown to significantly extend lifespan in several model organisms. Of all the genes that have been studied thus far, components of the insulin/IGF-1 signaling (IIS) pathway have emerged as the most robust regulators of longevity. In addition, IIS also regulates development, energy metabolism and the response to stress in a conserved manner. In Caenorhabditis elegans, signaling through this pathway is initiated by activation of the insulin/IGF-1 receptor tyrosine kinase DAF-2, which then activates a PI3-kinase ...


Elucidating The Transcriptional Network Underlying Expression Of A Neuronal Nicotinic Receptor Gene: A Dissertation, Michael D. Scofield Sep 2010

Elucidating The Transcriptional Network Underlying Expression Of A Neuronal Nicotinic Receptor Gene: A Dissertation, Michael D. Scofield

GSBS Dissertations and Theses

Neuronal nicotinic acetylcholine receptors (nAChRs) are involved in a plethora of fundamental biological processes ranging from muscle contraction to the formation of memories. The studies described in this work focus on the transcriptional regulation of the CHRNB4 gene, which encodes the ß4 subunit of neuronal nAChRs. We previously identified a regulatory sequence (5´– CCACCCCT –3´), or “CA box”, critical for CHRNB4 promoter activity in vitro. Here I report transcription factor interaction at the CA box along with an in vivo analysis of CA box transcriptional activity. My data indicate that Sp1, Sp3, Sox10 and c-Jun interact with the CHRNB4 CA ...


Elucidation Of The Multi-Faceted Roles Of The Sin (Septation Initiation Network); Understanding How The Sin Promotes Cytokinesis And Inhibits Interphase Growth In The Fission Yeast Schizosaccharomyces Pombe: A Dissertation, Samriddha Ray Aug 2010

Elucidation Of The Multi-Faceted Roles Of The Sin (Septation Initiation Network); Understanding How The Sin Promotes Cytokinesis And Inhibits Interphase Growth In The Fission Yeast Schizosaccharomyces Pombe: A Dissertation, Samriddha Ray

GSBS Dissertations and Theses

Cytokinesis is the cytoplasmic division of one cell into two independent daughter cells. Precise regulation of cytokinesis during cell cycle is essential for healthy and rapid multiplication of any organism. Schizosaccharomyces pombe has emerged as an excellent model system to study eukaryotic cell division regulation. This rod shaped organism grows by bipolar elongation in interphase when its actin cytoskeleton is concentrated at the cell ends (poles). However, growth stops in mitosis and the actin cytoskeleton is rearranged to facilitate assembly of the contractile actomyosin ring at the cell middle. Although several studies have focused on the separate processes of growth ...


A View Of The Imd Pathway From The Rhim, Kamna Aggarwal Mar 2010

A View Of The Imd Pathway From The Rhim, Kamna Aggarwal

GSBS Dissertations and Theses

Innate immunity is the first line of defense against invading pathogens. It functions to eliminate pathogens and also to control infections. The innate immune response is also important for the development of pathogen-specific adaptive immune responses. As a result, the study of innate immune signaling pathways is crucial for understanding the interactions between host and pathogen. Unlike mammals, insects lack a classical adaptive immune response and rely mostly on innate immune responses.

Innate immune mechanisms have been widely studied in the fruit fly, Drosophila melanogaster. The genetic and molecular tools available in the Drosophila system make it an excellent model ...


Regulation Of The Cdc14-Like Phosphatase Clp1 In Schizosaccharomyces Pombe And Identification Of Sid2 Kinase Substrates: A Dissertation, Chun-Ti Chen Nov 2009

Regulation Of The Cdc14-Like Phosphatase Clp1 In Schizosaccharomyces Pombe And Identification Of Sid2 Kinase Substrates: A Dissertation, Chun-Ti Chen

GSBS Dissertations and Theses

Coordination of mitosis and cytokinesis is crucial to generate healthy daughter cells with equal amounts of genetic and cytoplasmic materials. In the fission yeast Schizosaccharomyces pombe, an evolutionarily conserved Cdc14-like phosphatase (Clp1) functions to couple mitosis and cytokinesis by antagonizing CDK activity. The activity of Clp1 is thought to be regulated in part by its subcellular localization. It is sequestered in the nucleolus and the spindle pole body (SPB) during interphase. Upon mitotic entry, it is released into the cytoplasm and localized to the kinetochores, the actomyosin ring, and the mitotic spindle to carry out distinct functions. It is not ...


Worming To Complete The Insulin/Igf-1 Signaling Cascade: A Dissertation, Srivatsan Padmanabhan Apr 2009

Worming To Complete The Insulin/Igf-1 Signaling Cascade: A Dissertation, Srivatsan Padmanabhan

GSBS Dissertations and Theses

The insulin/IGF-1 signaling (IIS) was initially identified in C. elegansto control a developmental phenotype called dauer. Subsequently, it was realized that lifespan was extended by mutations in this pathway and became an intense focus of study. The IIS pathway regulates growth, metabolism and longevity across phylogeny and plays important roles in human disease such as cancer and diabetes. Given the large number of cellular processes that this pathway controls, understanding the regulatory mechanisms that modulate insulin/IGF-1 signaling is of paramount importance.

IIS signaling is a very well-studied kinase cascade but few phosphatases in the pathway are known ...


Role Of Wfs1 In Regulating Endoplasmic Reticulum Stress Signaling: A Dissertation, Sonya G. Fonseca Feb 2009

Role Of Wfs1 In Regulating Endoplasmic Reticulum Stress Signaling: A Dissertation, Sonya G. Fonseca

GSBS Dissertations and Theses

The endoplasmic reticulum (ER) is a multi-functional cellular compartment that functions in protein folding, lipid biosynthesis, and calcium homeostasis. Perturbations to ER function lead to the dysregulation of ER homeostasis, causing the accumulation of unfolded and misfolded proteins in the cell. This is a state of ER stress. ER stress elicits a cytoprotective, adaptive signaling cascade to mitigate stress, the Unfolded Protein Response (UPR). As long as the UPR can moderate stress, cells can produce the proper amount of proteins and maintain a state of homeostasis. If the UPR, however, is dysfunctional and fails to achieve this, cells will undergo ...


Role Of Map4k4 Signaling In Adipocyte And Macrophage Derived Inflammation: A Dissertation, Gregory J. Tesz Jul 2008

Role Of Map4k4 Signaling In Adipocyte And Macrophage Derived Inflammation: A Dissertation, Gregory J. Tesz

GSBS Dissertations and Theses

Human obesity is increasing globally at an impressive rate. The rise in obesity has led to an increase in diseases associated with obesity, such as type 2 diabetes. A major prerequisite for this disease is the development of insulin resistance in the muscle and adipose tissues. Interestingly, experiments in rodent models suggest that adipocytes and macrophages can profoundly influence the development of insulin resistance. Accordingly, the number of adipose tissue macrophages increases substantially during the development of obesity. Numerous research models have demonstrated that macrophages promote insulin resistance by secreting cytokines, like TNFα, which impair whole body insulin sensitivity and ...


Role Of Endoplasmic Reticulum Stress Response Signaling In T Cells: A Dissertation, Steven C. Pino Jul 2008

Role Of Endoplasmic Reticulum Stress Response Signaling In T Cells: A Dissertation, Steven C. Pino

GSBS Dissertations and Theses

T cells play a central role in cellular-mediated immunity and must become activated to participate as effector cells in the immune response. The activation process is highly intricate and involves stimulation of a number of downstream signaling pathways enabling T cells to proliferate and produce cytokines that are vital for proper effector function. This increase in protein production and protein folding activity adds to the normal physiological strain on cellular machinery. One cellular compartment that has generated a mechanism to mitigate the stress induced by increased protein production is the endoplasmic reticulum (ER).

In general, an increase in cellular production ...


Notch-1 And Igf-1 As Survivin Regulatory Pathways In Cancer: A Dissertation, Connie Wing-Ching Lee Jun 2008

Notch-1 And Igf-1 As Survivin Regulatory Pathways In Cancer: A Dissertation, Connie Wing-Ching Lee

GSBS Dissertations and Theses

The 21st century brought about a dramatic increase in knowledge about genetic and molecular profiles of cancer. This information has validated the complexity of tumor cells and increased awareness of “nodal proteins”, but has yet to advance the development of rational targeted cancer therapeutics. Nodal proteins are critical cellular proteins that collect biological inputs and distribute the information across diverse biological processes. Survivin acts as a nodal protein by interfacing the multiple signals involved in mitosis and apoptosis and functionally integrate proliferation, cell death, and cellular homeostasis. By characterizing survivin as a target of both Type 1 Insulin-like Growth ...


Plasma Membrane Localization Of Signaling Proteins In Yeast: A Dissertation, Satoe Takahashi May 2008

Plasma Membrane Localization Of Signaling Proteins In Yeast: A Dissertation, Satoe Takahashi

GSBS Dissertations and Theses

In response to external stimuli, many intracellular signaling proteins undergo dynamic changes in localization to the plasma membrane. Using the Saccharomyces cerevisiaemating pathway as a model, I investigated the molecular interactions that govern plasma membrane localization of signaling proteins, and how the plasma membrane compartmentalization of a signaling complex influences the overall signaling behavior of the pathway.

Signaling proteins often consist of multiple interaction domains that collectively dictate their localization and function. Ste20 is a p21-activated kinase (PAK) that functions downstream of the Rho-type GTPase Cdc42 to activate several mitogen-activated protein (MAP) kinase pathways in budding yeast, including the ...


Regulation Of The Nf-Кb Precursor Relish By The Drosophila I-Кb Kinase Complex: A Dissertation, Deniz Erturk Hasdemir May 2008

Regulation Of The Nf-Кb Precursor Relish By The Drosophila I-Кb Kinase Complex: A Dissertation, Deniz Erturk Hasdemir

GSBS Dissertations and Theses

The innate immune system is the first line of defense against infectious agents. It is essential for protection against pathogens and stimulation of long-term adaptive immune responses. Therefore, deciphering the mechanisms of the innate immune system is crucial for understanding the integrated systems of host defense against microbial infections, which is conserved from insects to humans.

Despite lacking a conventional adaptive immune system, insects can mount a robust immune response against a wide array of microbial pathogens. These innate immune mechanisms have been widely studied in Drosophila melanogaster, because of the model system’s powerful genetic, genomic and molecular tools ...


The Role Of Endoplasmic Reticulum Stress Signaling In Pancreatic Beta Cells: A Dissertation, Kathryn L. Lipson May 2008

The Role Of Endoplasmic Reticulum Stress Signaling In Pancreatic Beta Cells: A Dissertation, Kathryn L. Lipson

GSBS Dissertations and Theses

Protein folding in the endoplasmic reticulum (ER) is essential for proper cellular function. However, the sensitive environment in the ER can be perturbed by both pathological processes as well as by physiological processes such as a large biosynthetic load placed on the ER. ER stress is a specific type of intracellular stress caused by the accumulation of immature or abnormal misfolded or unfolded proteins in the ER. Simply defined, ER stress is a disequilibrium between ER load and folding capacity. Cells have an adaptive response that counteracts ER stress called the "Unfolded Protein Response” (UPR). The ability to adapt to ...


The Molecular Mechanisms Of Activity-Dependent Wingless (Wg)/Wnt Signaling At A Drosophila Glutamatergic Synapse: A Dissertation, Bulent Ataman Feb 2008

The Molecular Mechanisms Of Activity-Dependent Wingless (Wg)/Wnt Signaling At A Drosophila Glutamatergic Synapse: A Dissertation, Bulent Ataman

GSBS Dissertations and Theses

Synaptic plasticity, the ability of synapses to change in strength, underlies complex brain functions such as learning and memory, yet little is known about the precise molecular mechanisms and downstream signaling pathways involved. The major goal of my doctoral thesis was to understand these molecular mechanisms and cellular processes underlying synaptic plasticity using the Drosophilalarval neuromuscular junction (NMJ) as a model system.

My work centered on a signaling pathway, the Wg/Wnt signaling pathway, which was found to be crucial for activity-driven synapse formation. The Wg/Wnt family of secreted proteins, besides its well-characterized roles in embryonic patterning, cell ...


Surface Of Yersinia Pestis: Lcrv, F1 Production, Invasion And Oxygen: A Dissertation, Kimberly Lea Pouliot Dec 2007

Surface Of Yersinia Pestis: Lcrv, F1 Production, Invasion And Oxygen: A Dissertation, Kimberly Lea Pouliot

GSBS Dissertations and Theses

Of the eleven species of bacteria that comprise the genus Yersinia of the family Enterobacteriaceae, three species are pathogenic for humans. Yersinia pseudotuberculosis and Yersinia enterocolitica usually cause a mild, self-limiting mesenteric lymphadenitis or ileitis. Yersinia pestis causes a highly invasive often fatal disease known as plague. All three elaborate a type three secretion system that is essential for virulence and encoded on closely related plasmids. In Y. pestis, all the effectors, structural components and chaperones are encoded on the 70kb plasmid, pCD1.

Of these, LcrV from Y. enterocolitica has been implicated in playing an immunosuppressive role through its interaction ...


Rethinking Mechanisms Of Actin Pedestal Formation By Enteropathogenic Escherichia Coli In The Context Of Multiple Signaling Cascades: A Dissertation, Pamela Joyce Savage Feb 2007

Rethinking Mechanisms Of Actin Pedestal Formation By Enteropathogenic Escherichia Coli In The Context Of Multiple Signaling Cascades: A Dissertation, Pamela Joyce Savage

GSBS Dissertations and Theses

Enteropathogenic Escherichia coli (EPEC) is one of many bacterial and viral pathogens that can exploit the eukaryotic actin cytoskeleton for its own purposes. EPEC injects its own receptor, Tir, into the host cell plasma membrane where, upon binding the bacterial adhesin, intimin, can trigger actin assembly beneath bound bacteria resulting in characteristic actin "pedestals". The formation of these lesions is thought to be critical for bacterial colonization; and can also provide insight into actin dynamics of mammalian cells. EPEC Tir stimulates multiple signaling pathways converging on a central actin nucleation promoting factor, N-WASP. The best-characterized pathway of actin pedestal formation ...


Mechanisms Of Endocytic Sorting: A Dissertation, Deborah Marie Leonard Dec 2006

Mechanisms Of Endocytic Sorting: A Dissertation, Deborah Marie Leonard

GSBS Dissertations and Theses

Endocytosis is important for the regulation of signal transduction and for the movement of essential cellular components from outside the cell to their appropriate intracellular compartment(s). Two established mechanisms of endocytosis are clathrinmediated (CME) and clathrin-independent endocytosis, and they are responsible for internalization of different ligands. In this study, the newly established technique of total internal reflection fluorescent microscopy (TIRF-M) was used, along with standard biochemical and molecular biological tools, to systematically study the sorting and early trafficking of two established ligands of endocytosis, transferrin (Tf) and epidermal growth factor (EGF).

TIRF-M studies revealed that Tf binds its receptor ...


M1 Muscarinic Modulation Of N-Type Calcium Channels: A Dissertation, John F. Heneghan Nov 2006

M1 Muscarinic Modulation Of N-Type Calcium Channels: A Dissertation, John F. Heneghan

GSBS Dissertations and Theses

The influx of calcium through N-type calcium channels (N-current) affects a myriad of neuronal functions. These include the triggering of synaptic release of neurotransmitter, adjustment of membrane potential and changes in gene transcription. N-channels are highly modulated proteins, so that N-current is attenuated or potentiated in response to environmental changes. In turn, the modulation of N-current has a direct effect on the downstream events, making the N-channel a focal point in neural signaling, and its modulation a mechanism for short term plasticity.

The modulation of N-current by M1 muscarinic receptors (M1Rs) is of particular interest for several ...


Analysis Of Toll-Like Receptor 4 Signal Transduction And Irf3 Activation In The Innate Immune Response: A Dissertation, Daniel C. Rowe Jun 2006

Analysis Of Toll-Like Receptor 4 Signal Transduction And Irf3 Activation In The Innate Immune Response: A Dissertation, Daniel C. Rowe

GSBS Dissertations and Theses

Over the last decade, the innate immune system has been the subject of extensive research. Often overlooked by the robustness and specificity of the adaptive immune system, the innate immune system is proving to be just as complex. The identification of several families of pattern recognition receptors (PRRs) has revealed an ancient yet multifaceted system of proteins that are responsible for initiating host defense. A wide array of pathogens, from virus to bacteria, is detected using this assortment of receptors. One such family, the Toll-like receptors (TLRs), has been at the forefront of this research. To date, 10 TLRs have ...


The Role Of Tec Kinases In Cd4+ T Cell Activation: A Dissertation, Cheng-Rui Michael Li Oct 2005

The Role Of Tec Kinases In Cd4+ T Cell Activation: A Dissertation, Cheng-Rui Michael Li

GSBS Dissertations and Theses

The Tec family tyrosine kinases Itk, Tec and Rlk are expressed in T cells. Previous studies have established that these kinases are critical for TCR signaling, leading to the activation of PLCγ1. To further understand the functions of Tec kinases in T cell activation, we took three different approaches. First, we performed a thorough analysis of CD28-mediated signaling events and functional responses with purified naïve T cells from Itk-/- mice and a highly controlled stimulation system. Data from this set of studies definitively demonstrate that CD28 costimulation functions efficiently in naïve CD4+ T cells in the absence of Itk. Second ...


Cd4+ T Cell Responses: A Complex Network Of Activating And Tolerizing Signals As Revealed By Gene Expression Analysis: A Dissertation, David Spaulding Brown Sep 2005

Cd4+ T Cell Responses: A Complex Network Of Activating And Tolerizing Signals As Revealed By Gene Expression Analysis: A Dissertation, David Spaulding Brown

GSBS Dissertations and Theses

Immunologic self-tolerance is maintained by both central and peripheral mechanisms. Furthermore, regulation of mature lymphocyte responses is governed by inhibitory as well as stimulatory signals. TCR recognition of cognate peptide bound to MHC molecules provides the initial stimulus leading to T lymphocyte activation and determines the antigen specificity of any subsequent response. However, lymphocytes must discriminate between foreign and self antigens presented by self-MHC molecules to maintain self tolerance and avoid pathological autoimmunity. Consequently, TCR ligation alone is reported to result in abortive activation, T cell anergy, apoptosis, and tolerance. Under normal physiological conditions, costimulatory signals modify lymphocyte responsiveness to ...


Characterization Of Jnk Binding Proteins: A Dissertation, Jeffrey Scott Rogers Jul 2005

Characterization Of Jnk Binding Proteins: A Dissertation, Jeffrey Scott Rogers

GSBS Dissertations and Theses

The JNK signal transduction pathway mediates a broad, complex biological process in response to inflammatory cytokines and environmental stress. These responses include cell survival and apoptosis, proliferation, tumorigenesis and the immune response. The divergent cellular responses caused by the JNK signal transduction pathway are often regulated by spatial and cell type contexts, as well as the interaction with other cellular processes. The discovery of additional components of the JNK signal transduction pathway are critical to elucidate the stress response mechanisms in cells.

This thesis first discusses the cloning and characterization of two novel members of the JNK signal transduction pathway ...


Channel Specific Calcium Dynamics In Pc12 Cells: A Dissertation, Keith Tully May 2004

Channel Specific Calcium Dynamics In Pc12 Cells: A Dissertation, Keith Tully

GSBS Dissertations and Theses

Calcium ions (Ca2+) are involved in almost all neuronal functions, providing the link between electrical signals and cellular activity. This work examines the mechanisms by which a neuron can regulate the movement and sequestration of Ca2+ through specific channels such that this ubiquitous ion can encode specific functions. My initial focus was using intracellular calcium ([Ca2+]i) imaging techniques to study the influence of the inhibition of specific voltage gated calcium channels (VGCC) by ethanol on a depolarization induced rise in [Ca2+]i in neurohypophysial nerve terminals. This research took an unexpected turn when I observed ...


Pathways Linking Deregulated Proliferation To Apoptosis: A Dissertation, Harry A. Rogoff Apr 2004

Pathways Linking Deregulated Proliferation To Apoptosis: A Dissertation, Harry A. Rogoff

GSBS Dissertations and Theses

Proper regulation of cellular proliferation is critical for normal development and cancer prevention. Most, if not all, cancers contain mutations in the Rb/E2F pathway, which controls cellular proliferation. Inactivation of the retinoblastoma protein (Rb) can occur through Rb loss, mutation, or inactivation by cellular or viral oncoproteins leading to unrestrained proliferation. This occurs primarily by de-repression and activation of the E2F transcription factors, which promote the transition of cells from the G1to S phase of the cell cycle. In order to protect against loss of growth control, the p53 tumor suppressor is able to induce programmed cell ...


The Structural Basis For The Phosphorylation-Induced Activation Of Smad Proteins: A Dissertation, Benoy M. Chacko Feb 2004

The Structural Basis For The Phosphorylation-Induced Activation Of Smad Proteins: A Dissertation, Benoy M. Chacko

GSBS Dissertations and Theses

The Smad proteins transduce the signal of transforming growth factor-β (TGF-β) and related factors from the cell surface to the nucleus. Following C-terminal phosphorylation by a corresponding receptor kinase, the R-Smad proteins form heteromeric complexes with Smad4. These complexes translocate into the nucleus, bind specific transcriptional activators and DNA, ultimately modulating gene expression. Though studied through a variety of means, the stoichiometry of the R-Smad/Smad4 complex is unclear. We investigated the stoichiometry of the phosphorylation-induced R-Smad/Smad4 complex by using acidic amino acid substitutions to simulate phosphorylation. Size exclusion chromatography, analytical ultracentrifugation, and isothermal titration calorimetry analysis revealed that ...


The Regulation Of Nnos During Neuronal Differentiation And The Effect Of Nitric Oxide On Hdm2-P53 Binding: A Dissertation, Christopher M. Schonhoff Dec 2000

The Regulation Of Nnos During Neuronal Differentiation And The Effect Of Nitric Oxide On Hdm2-P53 Binding: A Dissertation, Christopher M. Schonhoff

GSBS Dissertations and Theses

Nitric oxide is a ubiquitous signaling molecule with both physiological and pathological functions in biological systems. Formed by the enzymatic conversion of arginine to citrulline, NO, has known roles in circulatory, immune and nervous tissues. In the nervous system nitric oxide has been implicated in long-term potentiation, neurotransmitter release, channel function, neuronal protection and neuronal degeneration. Much of our work has focused on yet another role for nitric oxide in cells, namely, neuronal differentiation.

During development, neuronal differentiation is closely coupled with cessation of proliferation. We use nerve growth factor (NGF)-induced differentiation of PC12 pheochromocytoma cells as a model ...


The Role Of Mkk3 In Mediating Signals To The P38 Map Kinase Pathway: A Dissertation, Mark Allen Wysk Nov 2000

The Role Of Mkk3 In Mediating Signals To The P38 Map Kinase Pathway: A Dissertation, Mark Allen Wysk

GSBS Dissertations and Theses

p38 mitogen-activated protein (MAP) kinases represent a subgroup of MAP kinases that respond to environmental stress and inflammatory cytokines. p38 MAPK is activated by two upstream kinases, MKK3 and MKK6, by dual phosphorylation on threonine and tyrosine in conserved kinase subdomain VII. Until recently the relative roles of MKK3 and MKK6 have remained unclear. I have undertaken two strategies in an effort to understand the importance of MKK3 as a p38 MAPK activator. First, I cloned and characterized the murine mkk3 gene and determined the structure of the 5'-terminus. Comparison of the murine and human mkk3 genes revealed that ...