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Phosphorylation

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Articles 1 - 30 of 31

Full-Text Articles in Cell Biology

Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial-Mesenchymal Transition In Cancer, Monserrat Olea-Flores, Miriam Daniela Zuniga-Eulogio, Miguel Angel Mendoza-Catalan, Hugo Alberto Rodriguez-Ruiz, Eduardo Castaneda-Saucedo, Carlos Ortuno-Pineda, Teresita Padilla-Benavides, Napoleon Navarro-Tito Jun 2019

Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial-Mesenchymal Transition In Cancer, Monserrat Olea-Flores, Miriam Daniela Zuniga-Eulogio, Miguel Angel Mendoza-Catalan, Hugo Alberto Rodriguez-Ruiz, Eduardo Castaneda-Saucedo, Carlos Ortuno-Pineda, Teresita Padilla-Benavides, Napoleon Navarro-Tito

Open Access Articles

Epithelial-mesenchymal transition (EMT) is a reversible cellular process, characterized by changes in gene expression and activation of proteins, favoring the trans-differentiation of the epithelial phenotype to a mesenchymal phenotype. This process increases cell migration and invasion of tumor cells, progression of the cell cycle, and resistance to apoptosis and chemotherapy, all of which support tumor progression. One of the signaling pathways involved in tumor progression is the MAPK pathway. Within this family, the ERK subfamily of proteins is known for its contributions to EMT. The ERK subfamily is divided into typical (ERK 1/2/5), and atypical (ERK 3/4 ...


Protein 14-3-3 (Ywha) Isoforms And Their Roles In Regulating Mouse Oocyte Maturation, Santanu De Aug 2018

Protein 14-3-3 (Ywha) Isoforms And Their Roles In Regulating Mouse Oocyte Maturation, Santanu De

Santanu De

The 14-3-3 (YWHA) is a highly conserved, ubiquitously expressed protein family regulating important cellular processes including cell cycle. This work, for the first time, explored the differential expression and roles of 14-3-3 isoforms during mouse oocyte maturation.

All seven mammalian 14-3-3 isoforms were identified in mouse eggs and ovarian follicular cells including oocytes, by Western blotting. Immunocytochemical and immunohistochemical staining confirmed the presence of all 14-3-3 isoforms in oocytes, eggs and ovarian follicles with characteristic similarities and differences in their distributions.

Mammalian oocytes are arrested at meiosis prophase I by an inhibitory phosphorylation on Cyclin-Dependent Kinase I (CDK1), released by ...


Structural And Functional Characterization Of Hyper-Phosphorylated Grk5 Protein Expressed From E. Coli, Joseph M. Krampen, John Tesmer, Qiuyan Chen Aug 2018

Structural And Functional Characterization Of Hyper-Phosphorylated Grk5 Protein Expressed From E. Coli, Joseph M. Krampen, John Tesmer, Qiuyan Chen

The Summer Undergraduate Research Fellowship (SURF) Symposium

G protein-coupled receptor (GPCR) kinases (GRKs) are proteins in the cell responsible for regulating GPCRs located on the cell membrane. GRKs regulate active GPCRs by phosphorylating them at certain sites which causes them to stop normal signaling on the membrane. This ultimately affects how the cell responds to its environment. GRK5 is a kinase of particular interest due to its involvement in the pathology of diseases such as cardiac failure, cancers, and diabetes. Understanding the structure and function of GRK5 is essential for discovering ways to manipulate its behavior with these diseases, but not much is known about how GRK5 ...


Casein Kinase 2-Mediated Phosphorylation Of Brahma-Related Gene 1 Controls Myoblast Proliferation And Contributes To Swi/Snf Complex Composition, Teresita Padilla-Benavides, Brian T. Nasipak, Amanda L. Paskavitz, Dominic T. Haokip, Jake M. Schnabl, Jeffrey A. Nickerson, Anthony N. Imbalzano Nov 2017

Casein Kinase 2-Mediated Phosphorylation Of Brahma-Related Gene 1 Controls Myoblast Proliferation And Contributes To Swi/Snf Complex Composition, Teresita Padilla-Benavides, Brian T. Nasipak, Amanda L. Paskavitz, Dominic T. Haokip, Jake M. Schnabl, Jeffrey A. Nickerson, Anthony N. Imbalzano

UMass Metabolic Network Publications

Transcriptional regulation is modulated in part by chromatin-remodeling enzymes that control gene accessibility by altering chromatin compaction or nucleosome positioning. Brahma-related gene 1 (Brg1), a catalytic subunit of the mammalian SWI/SNF chromatin-remodeling enzymes, is required for both myoblast proliferation and differentiation, and the control of Brg1 phosphorylation by calcineurin, PKCbeta1, and p38 regulates the transition to differentiation. However, we hypothesized that Brg1 activity might be regulated by additional kinases. Here, we report that Brg1 is also a target of casein kinase 2 (CK2), a serine/threonine kinase, in proliferating myoblasts. We found that CK2 interacts with Brg1, and mutation ...


Phopsphorylation And Ubiquitin Modification At Dna Damage Sites In Response To Double-Strand Breaks, Atanu Paul May 2017

Phopsphorylation And Ubiquitin Modification At Dna Damage Sites In Response To Double-Strand Breaks, Atanu Paul

UT GSBS Dissertations and Theses (Open Access)

Genomes of all organisms are continuously damaged by numerous exogenous and endogenous sources leading to different kinds of DNA lesions, which if not repaired efficiently may trigger wide-scale genomic instability, a hallmark of cancer development. To overcome this, cells have evolved a sophisticated sensory network called the DNA damage response (DDR) comprised of a large number of distinct protein complexes categorized as sensor, mediator, transducer and effector proteins that amplify the DNA damage signal and activate cell cycle checkpoint to initiate DNA repair or trigger apoptosis where the defect is beyond repair. This intricate signaling pathway is tightly regulated by ...


Tau Associates With Protein Tyrosine Phosphatase Shp2, Yohan Kim May 2017

Tau Associates With Protein Tyrosine Phosphatase Shp2, Yohan Kim

Theses and Dissertations

The microtubule-associated protein tau normally functions to bind to and stabilize microtubules. However, evidence now indicates that tau may also play a critical role in signaling pathways linked to neuronal development and neurodegeneration. The tau association with numerous signaling proteins such as tyrosine kinases, adaptor proteins, and scaffold proteins support this hypothesis. Phospho-Y18 tau was previously found in Alzheimer’s disease (AD) brain. Interestingly, this phosphorylation appeared to be regulated during neurodegeneration possibly by a tyrosine phosphatase(s). Identifying a candidate phosphatase, our lab found the association between tau and SHP2 in a neuronal cell line and dephosphorylation of phospho-Y18 ...


Key Virus-Host Interactions Required For Arenavirus Particle Assembly And Release, Christopher Michael Ziegler Jan 2017

Key Virus-Host Interactions Required For Arenavirus Particle Assembly And Release, Christopher Michael Ziegler

Graduate College Dissertations and Theses

Viruses are infectious agents that must infect the cells of living organisms in order to reproduce. They have relatively simple genomes which encode few proteins but can compensate for their simplicity by hijacking components of their cellular hosts. Arenaviruses, a family of zoonotic viruses carried by rodents, encode only 4 proteins. One of these proteins, Z, is responsible for several functions during the virus life cycle including driving the formation and release of new virus particles at the plasma membrane of infected cells. Relatively little is known about how this viral protein is regulated or the complement of host proteins ...


Defining The Role Of Phosphorylation And Dephosphorylation In The Regulation Of Gap Junction Proteins, Hanjun Li Dec 2016

Defining The Role Of Phosphorylation And Dephosphorylation In The Regulation Of Gap Junction Proteins, Hanjun Li

Theses & Dissertations

Gap junctions are intercellular channels that permit the free passage of ions, small metabolites, and signaling molecules between neighboring cells. In the diseased human heart, altered ventricular gap junction organization and connexin expression (i.e., remodeling) are key contributors to rhythm disturbances and contractile dysfunction. Connexin43 (Cx43) is the dominant gap junction protein isoform in the ventricle which is under tight regulation by serine/tyrosine phosphorylation. Phosphorylation and dephosphorylation regulate many aspects of Cx43 function including trafficking, assembly and disassembly, electrical and metabolic coupling at the plaque, as well as to modulate the interaction with other proteins.

Serine phosphorylation has ...


The Role Of Mdm2 Phosphorylation In P53 Responses To Dna Damage And Tumor Suppression: A Dissertation, Michael I. Carr Jul 2016

The Role Of Mdm2 Phosphorylation In P53 Responses To Dna Damage And Tumor Suppression: A Dissertation, Michael I. Carr

GSBS Dissertations and Theses

The p53 tumor suppressor protein is upregulated in response to DNA damage and other stress signals. The upregulation of p53 involves freeing it from negative regulation imposed by Mdm2 and MdmX (Mdm4). Accumulating evidence indicates that phosphorylation of Mdm proteins by different stress-activated kinases such as ATM or c-Abl significantly impacts p53 functions. We have previously shown that ATM phosphorylation of Mdm2 Ser394 is required for robust p53 stabilization and activation following DNA damage.

This dissertation describes in vivo examination of the mechanism by which Mdm2 Ser394 phosphorylation impacts p53 activities and its contribution to suppression of oncogene and DNA ...


Molecular Regulation Of Nox1 Nadph Oxidase In Vascular Smooth Muscle Cell Activation, Jennifer Lee Streeter May 2015

Molecular Regulation Of Nox1 Nadph Oxidase In Vascular Smooth Muscle Cell Activation, Jennifer Lee Streeter

Theses and Dissertations

Nox1 is of considerable importance because of its involvement in a wide variety of pathologies. Activation of Nox1 induces generation of reactive oxygen species (ROS) and cell migration, events critical for the pathogenesis of cardiovascular disease, amyotropic lateral sclerosis, gastrointestinal disease, immunological disorders, and multiple forms of cancer [1-8]. In order to best determine how to treat Nox1-mediated disease, we must gain a better understanding of the mechanisms that control Nox1 activation. Within the last decade, many studies have found that protein phosphorylation and protein trafficking are critical regulatory mechanisms that control the activation of multiple Nox proteins. Yet, to ...


Analysis Of The Candida Albicans Phosphoproteome, S. D. Willger, Z. Liu, R. A. Olarte, M. E. Adamo, J E. Stajich, L C. Myers, A N. Kettenbach, D A. Hogan Mar 2015

Analysis Of The Candida Albicans Phosphoproteome, S. D. Willger, Z. Liu, R. A. Olarte, M. E. Adamo, J E. Stajich, L C. Myers, A N. Kettenbach, D A. Hogan

Open Dartmouth: Faculty Open Access Scholarship

Candida albicans is an important human fungal pathogen in both immunocompetent and immunocompromised individuals. C. albicans regulation has been studied in many contexts, including morphological transitions, mating competence, biofilm forma- tion, stress resistance, and cell wall synthesis. Analysis of kinase- and phosphatase-deficient mutants has made it clear that pro- tein phosphorylation plays an important role in the regulation of these pathways. In this study, to further our understanding of phosphorylation in C. albicans regulation, we performed a deep analysis of the phosphoproteome in C. albicans. We identified 19,590 unique peptides that corresponded to 15,906 unique phosphosites on 2 ...


Myosin-Binding Protein C Corrects An Intrinsic Inhomogeneity In Cardiac Excitation-Contraction Coupling, Michael J. Previs, Benjamin L. Prosser, Ji Young Mun, Samantha Beck Previs, James Gulick, Kyounghwan Lee, Jeffrey Robbins, Roger Craig, W J. Lederer, David M. Warshaw Feb 2015

Myosin-Binding Protein C Corrects An Intrinsic Inhomogeneity In Cardiac Excitation-Contraction Coupling, Michael J. Previs, Benjamin L. Prosser, Ji Young Mun, Samantha Beck Previs, James Gulick, Kyounghwan Lee, Jeffrey Robbins, Roger Craig, W J. Lederer, David M. Warshaw

Cell and Developmental Biology Publications

The beating heart exhibits remarkable contractile fidelity over a lifetime, which reflects the tight coupling of electrical, chemical, and mechanical elements within the sarcomere, the elementary contractile unit. On a beat-to-beat basis, calcium is released from the ends of the sarcomere and must diffuse toward the sarcomere center to fully activate the myosin- and actin-based contractile proteins. The resultant spatial and temporal gradient in free calcium across the sarcomere should lead to nonuniform and inefficient activation of contraction. We show that myosin-binding protein C (MyBP-C), through its positioning on the myosin thick filaments, corrects this nonuniformity in calcium activation by ...


Altered Connexin 43 Expression Underlies Age-Dependent Decrease Of Regulatory T Cell Suppressor Function In Nonobese Diabetic Mice, Michel Kuczma, Cong-Yi Wang, Leszek Ignatowicz, Robert Gourdi, Piotr Kraj Jan 2015

Altered Connexin 43 Expression Underlies Age-Dependent Decrease Of Regulatory T Cell Suppressor Function In Nonobese Diabetic Mice, Michel Kuczma, Cong-Yi Wang, Leszek Ignatowicz, Robert Gourdi, Piotr Kraj

Biological Sciences Faculty Publications

Type 1 diabetes is one of the most extensively studied autoimmune diseases, but the cellular and molecular mechanisms leading to T cell–mediated destruction of insulin-producing β cells are still not well understood. In this study, we show that regulatory T cells (Tregs) in NOD mice undergo age-dependent loss of suppressor functions exacerbated by the decreased ability of activated effector T cells to upregulate Foxp3 and generate Tregs in the peripheral organs. This age-dependent loss is associated with reduced intercellular communication mediated by gap junctions, which is caused by impaired upregulation and decreased expression of connexin 43. Regulatory ...


Mdm2-Mediated Degradation Of Sirt6 Phosphorylated By Akt1 Promotes Tumorigenesis And Trastuzumab Resistance In Breast Cancer, Umadevi Thirumurthi Dec 2014

Mdm2-Mediated Degradation Of Sirt6 Phosphorylated By Akt1 Promotes Tumorigenesis And Trastuzumab Resistance In Breast Cancer, Umadevi Thirumurthi

UT GSBS Dissertations and Theses (Open Access)

Sirtuin6 (SIRT6) is one of the members of the Sirtuin family and functions as a longevity assurance gene by promoting genomic stability. It also regulates various cancer-associated pathways and was recently established as a bonafide tumor suppressor in colon cancer. This suggests that SIRT6 is an attractive target for pharmacological activation in cancer treatment, and hence, identification of potential regulators of SIRT6 would be an important and critical contribution towards cancer treatment. Here, we show that AKT1 phosphorylates SIRT6 at Ser338 and induces MDM2-SIRT6 interaction, priming SIRT6 for degradation via the MDM2-dependent ubiquitin-proteasome pathway. Blocking SIRT6 Ser338 phosphorylation ...


Traf2 Phosphorylation Regulates Cd40 Signaling To Facilitate B-Cell Lymphoma Progression, Lauren Michelle Workman Dec 2014

Traf2 Phosphorylation Regulates Cd40 Signaling To Facilitate B-Cell Lymphoma Progression, Lauren Michelle Workman

Theses and Dissertations

CD40 is a TNF-Receptor (TNFR) superfamily member that functions to promote several facets of the humoral immune response--including B cell proliferation, differentiation, antibody isotype switching, and cytokine expression. TNFR superfamily members lack intrinsic kinase activity and must recruit members of the TNFR-associated factor (TRAF) family of adaptor proteins to connect the receptor to intracellular signaling pathways. CD40-mediated JNK and NF-κB activation is critical for an intact humoral immune response; however, the precise mechanisms governing the spatiotemporal activation of these pathways are not completely understood.

In this study we report that CD40 ligation results in the dual phosphorylation of TRAF2 on ...


Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo Sep 2014

Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo

Katherine A. Fitzgerald

Emerging evidence suggests that innate immunity drives alcoholic liver disease (ALD) and that the interferon regulatory factor 3 (IRF3),a transcription factor regulating innate immune responses, is indispensable for the development of ALD. Here we report that IRF3 mediates ALD via linking endoplasmic reticulum (ER) stress with apoptotic signaling in hepatocytes. We found that ethanol induced ER stress and triggered the association of IRF3 with the ER adaptor, stimulator of interferon genes (STING), as well as subsequent phosphorylation of IRF3. Activated IRF3 associated with the proapoptotic molecule Bax [B-cell lymphoma 2 (Bcl2)-associated X protein] and contributed to hepatocyte apoptosis ...


Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo Sep 2014

Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo

Gyongyi Szabo

Emerging evidence suggests that innate immunity drives alcoholic liver disease (ALD) and that the interferon regulatory factor 3 (IRF3),a transcription factor regulating innate immune responses, is indispensable for the development of ALD. Here we report that IRF3 mediates ALD via linking endoplasmic reticulum (ER) stress with apoptotic signaling in hepatocytes. We found that ethanol induced ER stress and triggered the association of IRF3 with the ER adaptor, stimulator of interferon genes (STING), as well as subsequent phosphorylation of IRF3. Activated IRF3 associated with the proapoptotic molecule Bax [B-cell lymphoma 2 (Bcl2)-associated X protein] and contributed to hepatocyte apoptosis ...


Characterization Of Ca2+ Influx Pathway(S) During Mouse Oocyte Maturation, Banyoon Cheon Sep 2014

Characterization Of Ca2+ Influx Pathway(S) During Mouse Oocyte Maturation, Banyoon Cheon

Doctoral Dissertations

Ca2+ signaling induced at fertilization, also known as oscillations, is essential in mammalian eggs to initiate early embryonic development. The generation of the oscillations relies on optimization of Ca2+ toolkit components during oocyte maturation. In this dissertation, we intend to deepen our understanding of how this differentiation of the Ca2+ toolkit, especially those components associated with Ca2+ influx, is achieved during maturation, and how it contributes to the filling of the ER Ca2+ store during the maturation and fertilization.

We first identified the expression and characterized the function of the components of the Store Operated ...


Protein 14-3-3 (Ywha) Isoforms And Their Roles In Regulating Mouse Oocyte Maturation, Santanu De Jan 2014

Protein 14-3-3 (Ywha) Isoforms And Their Roles In Regulating Mouse Oocyte Maturation, Santanu De

Biology Faculty Books and Book Chapters

The 14-3-3 (YWHA) is a highly conserved, ubiquitously expressed protein family regulating important cellular processes including cell cycle. This work, for the first time, explored the differential expression and roles of 14-3-3 isoforms during mouse oocyte maturation.

All seven mammalian 14-3-3 isoforms were identified in mouse eggs and ovarian follicular cells including oocytes, by Western blotting. Immunocytochemical and immunohistochemical staining confirmed the presence of all 14-3-3 isoforms in oocytes, eggs and ovarian follicles with characteristic similarities and differences in their distributions.

Mammalian oocytes are arrested at meiosis prophase I by an inhibitory phosphorylation on Cyclin-Dependent Kinase I (CDK1), released by ...


Taking Shape : Regulating Mitochondria Morphology Through Alternative Splicing And Phosphorylation Of Fission Factor Proteins, Theodore James Wilson May 2013

Taking Shape : Regulating Mitochondria Morphology Through Alternative Splicing And Phosphorylation Of Fission Factor Proteins, Theodore James Wilson

Theses and Dissertations

Mitochondria are important cellular organelles whose functions include generation of ATP, sequestration and release of pro-apoptotic molecules and calcium buffering. Mitochondria function is tightly linked to organelle morphology, which exits in a dynamic spectrum between a highly interconnected/fused mitochondria network to a punctate/fragmented scattering of individual mitochondrion. A family of large GTPase enzymes modulates this spectrum, with fusion catalyzed through the actions of mitofusin 1 and 2 (Mfn1/2) on the outer mitochondria membrane (OMM) and optic atrophy 1 (Opa1) causing fusion of the inner mitochondria membrane (IMM). On the other end of the spectrum, fragmentation is catalyzed ...


Phosphorylation Of Histone Deacetylase 6 Within Its C-Terminal Region By Extracellular Signal Regulated Kinase 1, Kendra Allana Williams Jan 2013

Phosphorylation Of Histone Deacetylase 6 Within Its C-Terminal Region By Extracellular Signal Regulated Kinase 1, Kendra Allana Williams

Graduate Theses and Dissertations

http://upload.etdadmin.com/etdadmin/pdfout/222759_supp_undefined_2A63E500-E9D7-11E2-925E-BE522E1BA5B1.PDF


Phenotypic Analysis Of Schizosaccharomyces Pombe Strains Bearing Site-Directed Mutations In The Carboxy Terminal Domain Of The Largest Subunit Of Rna Polymerase Ii, Kyle S. Hoffman Aug 2012

Phenotypic Analysis Of Schizosaccharomyces Pombe Strains Bearing Site-Directed Mutations In The Carboxy Terminal Domain Of The Largest Subunit Of Rna Polymerase Ii, Kyle S. Hoffman

Electronic Thesis and Dissertation Repository

The phosphorylation status of the largest sub-unit of RNA polymerase II (Rpb1p) is crucial to the control of transcription in eukaryotes. The domain subject to this phosphorylation is known as the carboxyl terminal domain (CTD) and consists of multiple repeats (from 20 to 52 copies depending on the species in question) of the heptad sequence Y1S2P3T4S5P6S7. Interestingly, differential phosphorylation of S2, S5, and S7 residues is known to play an important role in the control of pre-mRNA processing. To determine the number of CTD ...


The Human Phosphotyrosine Signaling Network: Evolution And Hotspots Of Hijacking In Cancer., Lei Li, Chabane Tibiche, Cong Fu, Tomonori Kaneko, Michael F. Moran, Martin Schiller, Shawn Shun-Cheng Li, Edwin Wang Jul 2012

The Human Phosphotyrosine Signaling Network: Evolution And Hotspots Of Hijacking In Cancer., Lei Li, Chabane Tibiche, Cong Fu, Tomonori Kaneko, Michael F. Moran, Martin Schiller, Shawn Shun-Cheng Li, Edwin Wang

Life Sciences Faculty Publications

Phosphotyrosine (pTyr) signaling, which plays a central role in cell-cell and cell-environment interactions, has been considered to be an evolutionary innovation in multicellular metazoans. However, neither the emergence nor the evolution of the human pTyr signaling system is currently understood. Tyrosine kinase (TK) circuits, each of which consists of a TK writer, a kinase substrate, and a related reader, such as Src homology (SH) 2 domains and pTyr-binding (PTB) domains, comprise the core machinery of the pTyr signaling network. In this study, we analyzed the evolutionary trajectories of 583 literature-derived and 50,000 computationally predicted human TK circuits in 19 ...


Molecular Mechanisms Of Pre- And Postsynaptic Ephb/Ephrin-B Signaling In Synapse Formation And Function, Sean Isaac Sheffler-Collins Jan 2012

Molecular Mechanisms Of Pre- And Postsynaptic Ephb/Ephrin-B Signaling In Synapse Formation And Function, Sean Isaac Sheffler-Collins

Publicly Accessible Penn Dissertations

Proper function of the central nervous system relies on precise and coordinated cell-cell interactions and communication via synaptic transmission to assemble neuronal networks. Aberrant synaptic transmission is a hallmark of neuronal disease. The EphB family of receptor tyrosine kinases and their ephrin-B ligands play critical roles in the central nervous system in axon guidance, formation of pre- and post-synaptic specializations, localization of glutamate receptors, synaptic plasticity, and disease. EphB/ephrin-B signaling has been reported to modulate these processes, but the molecular mechanisms remain poorly understood. Our laboratory has previously shown that EphBs organize the formation of both pre- and postsynaptic ...


The Role Of Argininosuccinate Synthase Serine 328 Phosphorylation In Nitric Oxide Production, Ricci Haines Jan 2012

The Role Of Argininosuccinate Synthase Serine 328 Phosphorylation In Nitric Oxide Production, Ricci Haines

Graduate Theses and Dissertations

Until recently, the main mechanism of argininosuccinate synthase (AS) regulation was described to exist mainly at the level of transcription. Transcriptional regulation of AS has been shown to be coordinate with eNOS in response to shear stress, hypoxia, tumor necrosis factor á (TNF-á), and PPAR ã agonist troglitizone. However, it is now understood that one level of NO regulation is cellular control of arginine availability to eNOS via post-translational modifications of AS such as phosphorylation. The purpose of this investigation was to determine under what conditions AS is phosphorylated at S328, identify the pathway that AS phosphorylation at S328 plays ...


Phosphorylation Of The Glycine Transporter 1, Javier Vargas Medrano Jan 2010

Phosphorylation Of The Glycine Transporter 1, Javier Vargas Medrano

Open Access Theses & Dissertations

The extracellular levels of the neurotransmitter glycine in the brain are tightly regulated by the high-affinity glycine transporter 1 (GlyT1) and the clearance of glycine depends on its rate of transport and the levels of cell surface GlyT1. Over the past years, it has been shown that PKC activation diminishes the activity and promoted phosphorylation of several neurotransmitter transporters including the dopamine, serotonin and norepinephrine transporters however, its role is unknown for the glycine transporter. To get insights into the role of PKC activation on GlyT1 regulation, we used three N-terminus GlyT1 isoforms stably expressed in porcine aortic endothelial (PAE ...


Mtorc1 Hyperactivity Inhibits Serum Deprivation-Induced Apoptosis Via Increased Hexokinase Ii And Glut1 Expression, Sustained Mcl-1 Expression, And Glycogen Synthase Kinase 3Β Inhibition, Prashanth T. Bhaskar, Veronique Nogueira, Krushna C. Patra, Sang-Min Jeon, Youngkyu Park, R. Brooks Robey, Nissim Hay Sep 2009

Mtorc1 Hyperactivity Inhibits Serum Deprivation-Induced Apoptosis Via Increased Hexokinase Ii And Glut1 Expression, Sustained Mcl-1 Expression, And Glycogen Synthase Kinase 3Β Inhibition, Prashanth T. Bhaskar, Veronique Nogueira, Krushna C. Patra, Sang-Min Jeon, Youngkyu Park, R. Brooks Robey, Nissim Hay

Open Dartmouth: Faculty Open Access Scholarship

The current concept is that Tsc-deficient cells are sensitized to apoptosis due to the inhibition of Akt activity by the negative feedback mechanism induced by the hyperactive mTORC1. Unexpectedly, however, we found that Tsc1/2-deficient cells exhibit increased resistance to serum deprivation-induced apoptosis. mTORC1 hyperactivity contributes to the apoptotic resistance of serum-deprived Tsc1/2-deficient cells in part by increasing the growth factor-independent expression of hexokinase II (HKII) and GLUT1. mTORC1-mediated increase in hypoxia-inducible factor 1α (HIF1α) abundance, which occurs in the absence of serum in normoxic Tsc2-deficient cells, contributes to these changes. Increased HIF1α abundance in these cells is attributed ...


Analysis Of The Phosphorylated Forms Of Protein Kinase R, Christine Quartararo May 2009

Analysis Of The Phosphorylated Forms Of Protein Kinase R, Christine Quartararo

Honors Scholar Theses

Protein Kinase R (PKR) is induced by interferon and activated by dsRNA. Subsequent autophosphorylation and phosphorylation of eIF2alpha inhibits viral replication. In the latent state PKR exists as an unphosphorylated monomer. Work in the Cole laboratory has shown two additional states, a phosphorylated monomeric state (pPKRm) and a phosphorylated dimeric state (pPKRd). RNA serves as a scaffold bringing two PKRs together allowing dimerization and autophosphorylation to occur. The contribution of each state to the function of PKR remains unclear. Western blots were performed to examine the phosphorylation states of the essential residues,

T446 and T451. Activity assays have shown activation ...


Smooth Muscle Archvillin: A Novel Regulator Of Signaling And Contractility In Vascular Smooth Muscle, Samudra S. Gangopadhyay, Norio Takizawa, Cynthia Gallant, Amy L. Barber, Hyun-Dong Je, Tara C. Smith, Elizabeth J. Luna, Kathleen G. Morgan Mar 2008

Smooth Muscle Archvillin: A Novel Regulator Of Signaling And Contractility In Vascular Smooth Muscle, Samudra S. Gangopadhyay, Norio Takizawa, Cynthia Gallant, Amy L. Barber, Hyun-Dong Je, Tara C. Smith, Elizabeth J. Luna, Kathleen G. Morgan

Elizabeth J. Luna

The mechanisms by which protein kinase C (PKC) and extracellular-signal-regulated kinases (ERK1/2) govern smooth-muscle contractility remain unclear. Calponin (CaP), an actin-binding protein and PKC substrate, mediates signaling through ERK1/2. We report here that CaP sequences containing the CaP homology (CH) domain bind to the C-terminal 251 amino acids of smooth-muscle archvillin (SmAV), a new splice variant of supervillin, which is a known actin- and myosin-II-binding protein. The CaP-SmAV interaction is demonstrated by reciprocal yeast two-hybrid and blot-overlay assays and by colocalization in COS-7 cells. In differentiated smooth muscle, endogenous SmAV and CaP co-fractionate and co-translocate to the cell ...


Cellular Mechanisms Underlying Myogenic Reactivity In Isolated Arterioles, Hui Zou Jan 1995

Cellular Mechanisms Underlying Myogenic Reactivity In Isolated Arterioles, Hui Zou

Theses and Dissertations in Biomedical Sciences

The myogenic reactivity provides one of the principal mechanisms for blood flow autoregulation. The aims of the performed studies described in this dissertation were to test the role of [Ca2+]i and MLC phosphorylation in arteriolar myogenic reactivity and further examine the source(s) of activator Ca2+ required to initiate and maintain myogenic vasoconstriction. In addition, the possible underlying mechanism of contractile protein expression was also addressed.

These studies used male Sprague Dawley rats of 200 ~ 350 grams body weight. Experiments were carried out using rat cremaster first order arterioles and mesenteric vessels. Gel electrophoresis and immunoblotting techniques ...