Phosphorylation of Protein 4.1 on Tyrosine-418 Modulates Its Function
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Phosphorylation of Chicken Protein Tyrosine Phosphatase 1 by Casein Kinase II in Vitro
EXPERIMENTAL and MOLECULAR MEDICINE, Vol. 29, No 4, 229-233, December 1997 Phosphorylation of chicken protein tyrosine phosphatase 1 by casein kinase II in vitro Eun Joo Jung,1 Kee Ryeon Kang1 and Introduction Yoon-Se Kang1,2 The phosphorylation of protein tyrosine residues is an early event in signal transduction initiated by binding of 1 Department of Biochemistry and Gyeongsang Institute of Cancer growth factors and hormones to their cognate receptors Research, College of Medicine, Gyeongsang National University, and it leads to regulation of cellular activities which include Chinju 660-280, Korea proliferation, differentiation, and also malignant transfor- 2 Corresponding author mation of cells (Hunter, 1989; Ullirich and Schlessinger, Accepted 17 November 1997 1990; Cantley et al., 1991). Under normal conditions, the level of tyrosine phosphorylation within a cell is determined by a balance between the actions of protein tyrosine Abbreviations: CPTP, chicken protein tyrosine phosphatase; HPTP1B, human placenta kinases (PTKs) and protein tyrosine phosphatases (PTPs) protein tyrosine phosphatase 1B; CKII, casein kinase II; MAP kinase, mitogen-activated (Hunter, 1989; Fischer et al., 1991; Trowbridge, 1991). protein kinase; GST, glutathione S-transferase; pNPP, p-nitrophenyl phosphate; EGF, PTPs do not simply reverse the action of tyrosine kinases, epidermal growth factor but rather, PTP itself may play a central role in cellular regulation. PTPs are generally classified as transmem- brane (receptor-type) and nontransmembrane (nonrecep- tor-type) enzymes based on the presence or absence of extracellular and transmembrane portions of their predicted sequence (Fischer et al., 1991). Because the activity of Abstract tyrosine kinase can be controlled by phosphorylation, it has been postulated that PTP activity may be regulated The phosphorylation and dephosphorylation of by phosphorylation as well. -
Casein Kinase 1 Isoforms in Degenerative Disorders
CASEIN KINASE 1 ISOFORMS IN DEGENERATIVE DISORDERS DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Theresa Joseph Kannanayakal, M.Sc., M.S. * * * * * The Ohio State University 2004 Dissertation Committee: Approved by Professor Jeff A. Kuret, Adviser Professor John D. Oberdick Professor Dale D. Vandre Adviser Professor Mike X. Zhu Biophysics Graduate Program ABSTRACT Casein Kinase 1 (CK1) enzyme is one of the largest family of Serine/Threonine protein kinases. CK1 has a wide distribution spanning many eukaryotic families. In cells, its kinase activity has been found in various sub-cellular compartments enabling it to phosphorylate many proteins involved in cellular maintenance and disease pathogenesis. Tau is one such substrate whose hyperphosphorylation results in degeneration of neurons in Alzheimer’s disease (AD). AD is a slow neuroprogessive disorder histopathologically characterized by Granulovacuolar degeneration bodies (GVBs) and intraneuronal accumulation of tau in Neurofibrillary Tangles (NFTs). The level of CK1 isoforms, CK1α, CK1δ and CK1ε has been shown to be elevated in AD. Previous studies of the correlation of CK1δ with lesions had demonstrated its importance in tau hyperphosphorylation. Hence we investigated distribution of CK1α and CK1ε with the lesions to understand if they would play role in tau hyperphosphorylation similar to CK1δ. The kinase results were also compared with lesion correlation studies of peptidyl cis/trans prolyl isomerase (Pin1) and caspase-3. Our results showed that among the enzymes investigated, CK1 isoforms have the greatest extent of colocalization with the lesions. We have also investigated the distribution of CK1α with different stages of NFTs that follow AD progression. -
Mechanism of Insulin Receptor Kinase Inhibition in Non-Insulin- Dependent Diabetes Mellitus Patients
Mechanism of insulin receptor kinase inhibition in non-insulin- dependent diabetes mellitus patients. Phosphorylation of serine 1327 or threonine 1348 is unaltered. M Kellerer, … , K Siddle, H U Häring J Clin Invest. 1995;96(1):6-11. https://doi.org/10.1172/JCI118073. Research Article The tyrosine kinase activity of insulin receptor isolated from the skeletal muscle of NIDDM patients has previously been found to be decreased compared with the activity of receptor from nondiabetic subjects but the mechanism underlying this defect is unknown. Phosphorylation of receptor serine/threonine residues has been proposed to exert an inhibitory influence on receptor tyrosine kinase activity and Ser 1327 and Thr 1348 have been identified as specific sites of phosphorylation in the insulin receptor COOH terminal domain. To address the potential negative regulatory role of phosphorylation of these residues in vivo, we assessed the extent of phosphorylation of each site in insulin receptor isolated from the skeletal muscle of 12 NIDDM patients and 13 nondiabetic, control subjects. Phosphorylation of Ser 1327 and Thr 1348 was determined using antibodies that specifically recognize insulin receptor phosphorylated at these sites. In addition, a phosphotyrosine-specific antibody was used to monitor receptor tyrosine phosphorylation. The extent of insulin-induced tyrosine autophosphorylation was decreased in receptor isolated from diabetic versus nondiabetic muscle, thus confirming earlier reports. In contrast, there was no significant difference in the extent of phosphorylation of either Ser 1327 or Thr 1348 in receptor isolated from diabetic or nondiabetic muscle as assessed by immunoprecipitation (Ser 1327: 5.6 +/- 1.6% diabetics vs. 4.7 +/- 2.0% control; Thr 1348: 3.8 +/- 1.0% diabetics vs. -
MP Kinase (Phosphoprotein) Assay
MSD® MAP Kinase Phosphoprotein Assay: Whole Cell Lysate Kit For quantitative determination of phosphorylated p38(Thr180/Tyr182), ERK1/2 (Thr202/Tyr204; Thr185/Tyr187), and JNK (Thr183/Tyr185) in human, mouse, and rat whole cell lysate samples Alzheimer’s Disease Angiogenesis BioProcess Cardiac 1. Phospho-p38 Cell Signaling 2. BSA blocked Clinical Immunology 3. Phospho-JNK Cytokines 4. Phospho-ERK1/2 Growth Factors Hypoxia Immunogenicity Inflammation Metabolic MAP (Mitogen-Activated Protein) kinases are a family of evolutionarily conserved eukaryotic serine/threonine protein kinases which link Oncology receptors on the cell surface to important intracellular regulatory targets. MAP kinases also elicit an intracellular effect in response to physical and Toxicology chemical cellular stress. MAP kinase cascades within the cell are composed of a series of proteins, the first of which is a MAP kinase kinase kinase Vascular (MAPKKK).1 The MAPKKK is activated by phosphorylation in response to growth factors, mitogens, inflammatory cytokines, G-protein coupled receptors (GPCRs) or stress. The MAPKKK in turn phosphorylates MAPKK, which then phosphorylates MAPK.2 The activated terminal MAPK translocates into the nucleus, thereby exerting an effect on gene transcription. Through these pathways, the cell regulates responses leading to cell Catalog Numbers proliferation and differentiation, development, inflammation, and cell survival or apoptosis.2 ERK1/2, p38, and JNK are all MAP kinases, activated by the MAPK kinases MEK1/2, MKK3/6, and MKK4/7, respectively.2 Because these pathways are critical for the regulation of cell growth and survival, MAP Kinase 3 Phosphoprotein Assay: the MAP kinase family of enzymes offers desirable targets for the development of anti-cancer therapeutics. -
1519038862M28translationand
Paper No. : 15 Molecular Cell Biology Module : 28 Translation and Post-translation Modifications in Eukaryotes Development Team Principal Investigator : Prof. Neeta Sehgal Department of Zoology, University of Delhi Co-Principal Investigator : Prof. D.K. Singh Department of Zoology, University of Delhi Paper Coordinator : Prof. Kuldeep K. Sharma Department of Zoology, University of Jammu Content Writer : Dr. Renu Solanki, Deen Dayal Upadhyaya College Dr. Sudhida Gautam, Hansraj College, University of Delhi Mr. Kiran K. Salam, Hindu College, University of Delhi Content Reviewer : Prof. Rup Lal Department of Zoology, University of Delhi 1 Molecular Genetics ZOOLOGY Translation and Post-translation Modifications in Eukaryotes Description of Module Subject Name ZOOLOGY Paper Name Molecular Cell Biology; Zool 015 Module Name/Title Cell regulatory mechanisms Module Id M28: Translation and Post-translation Modifications in Eukaryotes Keywords Genome, Proteome diversity, post-translational modifications, glycosylation, phosphorylation, methylation Contents 1. Learning Objectives 2. Introduction 3. Purpose of post translational modifications 4. Post translational modifications 4.1. Phosphorylation, the addition of a phosphate group 4.2. Methylation, the addition of a methyl group 4.3. Glycosylation, the addition of sugar groups 4.4. Disulfide bonds, the formation of covalent bonds between 2 cysteine amino acids 4.5. Proteolysis/ Proteolytic Cleavage 4.6. Subunit binding to form a multisubunit protein 4.7. S-nitrosylation 4.8. Lipidation 4.9. Acetylation 4.10. Ubiquitylation 4.11. SUMOlytion 4.12. Vitamin C-Dependent Modifications 4.13. Vitamin K-Dependent Modifications 4.14. Selenoproteins 4.15. Myristoylation 5. Chaperones: Role in PTM and mechanism 6. Role of PTMs in diseases 7. Detecting and Quantifying Post-Translational Modifications 8. -
The Structure and Mechanism of Phosphoprotein Phosphatases Many Phosphatases Require Two Metal Ions for Catalysis
WILLIAM P TAYLOR AND THEODORE S WIDLANSKI MINIREVIEW Charged with meaning: the structure and mechanism of phosphoprotein phosphatases Many phosphatases require two metal ions for catalysis. New structural information on two serinekhreonine phosphatases offers insight into how the metals contribute to catalysis. A comparison with the structures of protein tyrosine phosphatases, which do not use metal ions, shows that the only similarity at the active site is that of charge. Chemistry & Biology November 1995, 2:713-718 Many biological processes are regulated by J simple substrates; and (3) small-molecule specific - enzymes chcniical event - the cleavage or formation of phos- that hydrolyze one (or a group of structurally similar) phdte esters. In nature, these reactions are catalyzed by substrate(s), for example, phosphoinocitol nlonophos- tv,m sets of enzynws, phosphatases and kinnses. Kinases phatasc (this cnzyrne may be the clinical target of operate in the synthetic direction (phocphorylation) lithium ion therapy for depression [A]). while phosphatases catalyze the hydrolysis (cleavage) reaction. Over the last decade there has been a growing A second useful classification scheme is our according rcalizCition that phosphataws are extremely important in to the enzyme’s mechanism of action. Some phos- ccllulx and organismal functions [ 1 1. Here, we focus on phatascs use an active site nucleophile 3s the initi,J recent Ed\-antes in our understanding of phosphatases. phosphoryl group acceptor; others transfer it inuned- especially phosphoprotein phosphatases, with J vielv to atcly to water (Fig. 3). The first group cm be further clarifyiiig some of the mrchanictic and structural con- subdivided according to the phosphoryl group acceptor plcsitie and mlbiguities presented by this diverse group (cysteine. -
The Role of Casein Kinase 1 in Meiosis
e & Ch m rom ro o d s n o y m S Zhao and Liang, J Down Syndr Chr Abnorm 2016, 2:1 e n A Journal of Down Syndrome & w b o n DOI: 10.4172/2472-1115.1000106 D o f r m o l ISSN: 2472-1115a a l i n t r i e u s o J Chromosome Abnormalities Review Article Open Access The Role of Casein Kinase 1 in Meiosis Yue-Fang Zhao and Cheng-Guang Liang* The Key Laboratory of National Education Ministry for Mammalian Reproductive Biology and Biotechnology, The Research Center for Laboratory Animal Science, College of Life Science, Inner Mongolia University, Hohhot, Inner Mongolia, People’s Republic of China Abstract The casein kinase 1 (CK1) belongs to the serine/threonine protein kinases. CK1 members, which commonly exist in all eukaryotes, are involved in the regulation of many cellular processes linked to cell cycle progression, spindle- dynamics, and chromosome segregation. Additionally, CK1 regulate key signaling pathways such as Wnt (Wingless/ Int-1), Hh (Hedgehog), and Hippo, known to be critically involved in tumor progression. Considering the importance of CK1 for accurate cell division and regulation of tumor suppressor functions, it is not surprising scientific effort has enormously increased. In mammals, CK1 regulate the transition from interphase to metaphase in mitosis. In budding yeast and fission yeast, CK1 phosphorylate Rec8 subunits of cohesin complex and regulate chromosome segregation in meiosis. During meiosis, two rounds of chromosome segregation after a single round of DNA replication produce haploid gametes from diploid precursors. Any mistake in chromosome segregation may result in aneuploidy, which in meiosis are one of the main causes of infertility, abortion and many genetic diseases in humans. -
Phosphorylation by Cellular Casein Kinase II Is Essential For
Proc. Natl. Acad. Sci. USA Vol. 89, pp. 6570-6574, July 1992 Biochemistry Phosphorylation by cellular casein kinase II is essential for transcriptional activity of vesicular stomatitis virus phosphoprotein P (protein phosphorylation/casein kinase il/transcripfion) SAILEN BARIK* AND AMIYA K. BANERJEE Department of Molecular Biology, Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195-5069 Communicated by W. K. Joklik, April 3, 1992 ABSTRACT We have previously shown that phosphory- kinases revealed that they were distinct and different from latfon of vesicular stomatitis virus (VSV) phosphoprotein P by each other. In this communication, we report the purification cellular protein kinase activity is an essential prerequisite for its and detailed characterization of the cellular protein kinase transcriptional function. We have now purified this protein and show that it is a single enzyme with properties identical kinase by monitoring its ability to phosphorylate bacterially to that ofcellular casein kinase II (CKII). Phosphorylation of expressed, unphosphorylated P protein. Biochemical studies the phosphate-free P protein (PO) by purified CKII and L showed that the kinase is indi uihable from casein kinase kinase in vitro fully restored transcriptional activity of P H, a ubiquitous cyclic AMP-independent protein kinase pres- protein. ent in a wide variety ofeukaryotic cells and tissues. Functional VSV transcription could be reconstituted with viral L protein, N-RNA template, and P protein phosphorylated by either MATERIALS AND METHODS purified cellular protein kinase or purified casein kinase Il. The Viral (VSV, New Jersey serotype, Ogden subtype) L protein unusual role of casein kinase II in the transcription process of and N-RNA template and bacterially expressed P protein of a nonsegmented negative-strand RNA virus would have im- the same serotype were purified as described (3). -
Stability of Phosphoprotein As a Biological Marker of Tumor Signaling Amanda F
Imaging, Diagnosis, Prognosis Stability of Phosphoprotein as a Biological Marker of Tumor Signaling Amanda F. Baker,1Tomislav Dragovich,1Nathan T.Ihle,1RyanWilliams,1 Cecilia Fenoglio-Preiser,2 and Garth Powis1 Abstract Purpose:The purpose of the study was to evaluate the stability of phosphoprotein as a marker of signaling activity in human tumors using clinical samples and xenografts. Experimental Design: The expression of phospho-Ser473-Akt (p-Akt) was assessed by immunohistochemistry in paraffin-embedded samples from patients enrolled in a Southwest Oncology Group clinical trial of gastroesophageal junction tumors and by immunohistochemistry and Western blotting in human colon tumor xenografts at various times after removal from the animal. Results: Clinical samples had evaluable p-Akt staining only when obtained as biopsies (9 of 13) and no staining was observed in tumors obtained as surgically resected samples (0 of 15). In HT- 29 colon cancer xenografts, p-Akt staining was present in fresh sample but not in tissue that had been allowed to stand for 30 minutes at room temperature.Western blotting of HT-29 tumor xen- ografts at room temperature showed a slow decrease in total Akt with a half-life of 180 minutes and a rapid decrease in p-Akt with a half-life of 20 minutes. Conclusions: Caution should be used when using phosphoprotein levels in human tumor speci- mens to measure intrinsic signaling activity or drug effects because of the potential for rapid de- phosphorylation. Rapid processing of biopsies is essential and postoperative surgical samples may be of limited value because of the time to fixation. -
Structure, Function and Evolution of Phosphoprotein P0 and Its Unique Insert in Tetrahymena Thermophila
University of Rhode Island DigitalCommons@URI Open Access Master's Theses 2014 STRUCTURE, FUNCTION AND EVOLUTION OF PHOSPHOPROTEIN P0 AND ITS UNIQUE INSERT IN TETRAHYMENA THERMOPHILA Giovanni Pagano University of Rhode Island, [email protected] Follow this and additional works at: https://digitalcommons.uri.edu/theses Recommended Citation Pagano, Giovanni, "STRUCTURE, FUNCTION AND EVOLUTION OF PHOSPHOPROTEIN P0 AND ITS UNIQUE INSERT IN TETRAHYMENA THERMOPHILA" (2014). Open Access Master's Theses. Paper 358. https://digitalcommons.uri.edu/theses/358 This Thesis is brought to you for free and open access by DigitalCommons@URI. It has been accepted for inclusion in Open Access Master's Theses by an authorized administrator of DigitalCommons@URI. For more information, please contact [email protected]. STRUCTURE, FUNCTION AND EVOLUTION OF PHOSPHOPROTEIN P0 AND ITS UNIQUE INSERT IN TETRAHYMENA THERMOPHILA BY GIOVANNI PAGANO A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE IN BIOLOGICAL AND ENVIRONMENTAL SCIENCES UNIVERSITY OF RHODE ISLAND 2014 MASTER OF SCIENCE OF GIOVANNI PAGANO APPROVED: Thesis Committee: Major Professor Linda A. Hufnagel Lenore M. Martin Roberta King Nasser H. Zawia DEAN OF THE GRADUATE SCHOOL UNIVERSITY OF RHODE ISLAND 2014 ABSTRACT Phosphoprotein P0 is a highly conserved ribosomal protein that forms the central scaffold of the large ribosomal subunit’s “stalk complex”, which is necessary for recruiting protein elongation factors to the ribosome. Evidence in the literature suggests that P0 may be involved in diseases such as malaria and systemic lupus erythematosus. We are interested in the possibility that the P0 of the “ciliated protozoa” Tetrahymena thermophila may be useful as a model system for vaccine research and drug development. -
Tyrosine Kinases Play a Permissive Role in Glucose-Induced Insulin Secretion from Adult Rat Islets
19 Tyrosine kinases play a permissive role in glucose-induced insulin secretion from adult rat islets S J Persaud, T E Harris, C J Burns and P M Jones Cellular and Molecular Endocrinology Group, Biomedical Sciences Division, King’s College London, Campden Hill Road, London W8 7AH, UK (Requests for offprints should be addressed to S J Persaud) ABSTRACT The role(s) played by protein tyrosine kinases (TA47) inhibited islet tyrosine kinase activities (PTKs) in the regulation of insulin secretion from and glucose-, 4á ketoisocaproic acid (KIC)- and pancreatic â cells is not clear. We have examined the sulphonylurea-stimulated insulin release, without effects of glucose, the major physiological insulin affecting glucose metabolism. GS and TA47 also secretagogue, on the tyrosine phosphorylation state inhibited protein serine/threonine kinase activities of islet proteins, and assessed â cell insulin secretory to a limited extent, but had no effect on Ca2+, cyclic responses in the presence of PTK inhibitors. Under AMP- or phorbol myristate acetate (PMA)-induced basal conditions islets contained many proteins insulin secretion from electrically permeabilised phosphorylated on tyrosine residues, and glucose islets. These results suggest that PTK inhibitors (20 mM; 5–15 min) was without demonstrable effect exert their inhibitory effects on insulin secretion on the pattern of tyrosine phosphorylation, in either proximal to Ca2+ entry and it is proposed that the absence or presence of the protein tyrosine they act at the site of the voltage-dependent Ca2+ phosphatase (PTP) inhibitor, sodium pervanadate channel which regulates Ca2+ influx into â cells (PV). PV alone (100 µM) increased tyrosine following nutrient- and sulphonylurea-induced phosphorylation of several islet proteins. -
SNT, a Differentiation-Specific Target of Neurotrophic Factor-Induced Tyrosine Kinase Activity in Neurons and PC12 Cells STUART J
MOLECULAR AND CELLULAR BIOLOGY, Apr. 1993, p. 2203-2213 Vol. 13, No. 4 0270-7306/93/042203-11$02.00/0 Copyright ) 1993, American Society for Microbiology SNT, a Differentiation-Specific Target of Neurotrophic Factor-Induced Tyrosine Kinase Activity in Neurons and PC12 Cells STUART J. RABIN, VAUGHN CLEGHON, ANtD DAVID R. KAPLAN* Eukaryotic Signal Transduction Group, Molecular Mechanisms of Carcinogenesis Laboratory, ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, P.O. Box B, Frederick, Maryland 21702-1201 Received 23 October 1992/Returned for modification 26 November 1992/Accepted 26 January 1993 To elucidate the signal transduction mechanisms used by ligands that induce differentiation and the cessation of cell division, we utilized p13 uc1agarose, a reagent that binds p34C2/cdk2 By using thi re t identified a 78- to 90-kDa species in PC12 pheochromocytoma cells that is rapidly phosphorylated on tyrosine following treatment with the differentiation factors nerve growth factor (NGF) and fibroblast growth factor but not by the mitogens epidermal growth factor or insulin. This species, called SNT (suc-associated neurotrophic factor-induced tyrosine-phosphorylated target), was also phosphorylated on tyrosine in primary rat cortical neurons treated with the neurotrophic factors neurotrophin-3, brain-derived neurotrophic factor, and fibroblast growth factor but not in those treated with epidermal growth factor. In neuronal and fibroblast cells, where NGF can also act as a mitogen, SNT was tyrosine phosphorylated to a much greater extent during NGF-induced differentiation than during NGF-induced proliferation. SNT was phosphorylated in vitro on serine, threonine, and tyrosine in pl3sucl-agarose precipitates from NGF-treated PC12 cells, indicating that this protein may be a substrate of kinase activities associated with p13suc1-p34cdc21cdk2 complexes.