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Genomes and Genes | S B ShearsSummaryAffiliation: National Institutes of Health Country: USA Publications
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The versatility of inositol phosphates as cellular signalsS B Shears
Inositide Signalling Section, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
Biochim Biophys Acta 1436:49-67. 1998..Therefore, this review assesses the evidence that inositol phosphates have evolved into a versatile family of second messengers...
Intracellular localization of human Ins(1,3,4,5,6)P5 2-kinaseMaria A Brehm
NIEHS NIH, 111 T W Alexander Drive, Research Triangle Park, NC 27709, USA
Biochem J 408:335-45. 2007..By site-directed mutagenesis we identified a nuclear import signal and a peptide segment mediating the nuclear export of IP5K...- Diphosphoinositol polyphosphates: what are the mechanisms?Stephen B Shears
Inositol Signaling Group, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA
Adv Enzyme Regul 51:13-25. 2011..Reflecting our expectations of all teenagers, it should be our earnest hope that in the near future the diphosphoinositol polyphosphates will finally grow up... - Structural insight into inositol pyrophosphate turnoverStephen B Shears
Inositol Signaling Group, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, PO Box 12233, NC 27709, USA Electronic address
Adv Biol Regul 53:19-27. 2013..This work includes the analysis of crystal complexes with substrates, products, transition state analogs, and a novel phosphonoacetate substrate analog... - Functional regulation of ClC-3 in the migration of vascular smooth muscle cellsSindura B Ganapathi
Inositol Signaling Group, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA
Hypertension 61:174-9. 2013..These cell-signaling roles of ClC-3 in VSMC migration suggest new therapeutic approaches to vascular remodeling diseases... 
Defining signal transduction by inositol phosphatesStephen B Shears
Inositol Signaling Section, Laboratory of Signal Transduction, NIEHS, NIH, DHHS, Research Triangle Park, 27709, NC, USA, USA
Subcell Biochem 59:389-412. 2012..e. its function is not stimulus-dependent) do not satisfy our signaling criteria. We conclude that Ins(3,4,5,6)P(4) is, to date, the only Ins(1,4,5)P(3) metabolite that has been validated to act as a second messenger...- Assessing the omnipotence of inositol hexakisphosphateS B Shears
Inositol Signaling Section, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, 27709, Research Triangle Park, NC, USA
Cell Signal 13:151-8. 2001..Indeed, many of the proposed cellular functions of InsP(6) cannot sustain a challenge from the implementation of a rigorous set of criteria, which are designed to avoid experimental artefacts... - Diphosphoinositol polyphosphates: metabolic messengers?Stephen B Shears
Inositide Signaling Group, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA
Mol Pharmacol 76:236-52. 2009..This review will also discuss the latest proposals concerning possible molecular mechanisms of action of this intriguing class of molecules... - How versatile are inositol phosphate kinases?Stephen B Shears
Inositol Signaling Section, Laboratory of Signal Transduction, NIEHS NIH DHSS Research Triangle Park, NC 27709, USA
Biochem J 377:265-80. 2004.... - Cell signaling by a physiologically reversible inositol phosphate kinase/phosphataseStephen B Shears
Laboratory of Signal Transduction, Inositol Signaling Section, National Institute of Environmental Health Sciences, NIH/DHHS, Research Triangle Park, NC 27709, USA
Adv Enzyme Regul 44:265-77. 2004 - Telomere maintenance by intracellular signals: new kid on the block?Stephen B Shears
Inositol Signaling Group, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, P O Box 12233, Research Triangle Park, NC 27709, USA
Proc Natl Acad Sci U S A 102:1811-2. 2005 - Rounding up the usual suspects: protein kinases as therapeutic targetsStephen B Shears
Inositol Signaling Section, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
Drug Discov Today 10:240-2. 2005..Signal Transduction: Targets for Effective Therapeutics. Conference held 8-9 November 2004, in Seaport Hotel, Boston, MA, USA... - Can intervention in inositol phosphate signalling pathways improve therapy for cystic fibrosis?Stephen B Shears
Inositol Phosphate Signaling Group, NIEHS NIH DHHS, Research Triangle Park, NC 27709, USA
Expert Opin Ther Targets 9:1307-17. 2005..One member of this drug family (INO-4995; Inologic) was recently shown to inhibit ENaC, thereby reducing fluid absorbtion by airway epithelial cells... - Site-directed mutagenesis of diphosphoinositol polyphosphate phosphohydrolase, a dual specificity NUDT enzyme that attacks diadenosine polyphosphates and diphosphoinositol polyphosphatesX Yang
Inositide Signaling Group, Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
J Biol Chem 274:35434-40. 1999..This new information helps define DIPP's structural, functional, and evolutionary relationships to Nudix hydrolases... - The diadenosine hexaphosphate hydrolases from Schizosaccharomyces pombe and Saccharomyces cerevisiae are homologues of the human diphosphoinositol polyphosphate phosphohydrolase. Overlapping substrate specificities in a MutT-type proteinS T Safrany
Inositide Signaling Group, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
J Biol Chem 274:21735-40. 1999.... - Expanding coincident signaling by PTEN through its inositol 1,3,4,5,6-pentakisphosphate 3-phosphatase activityJ J Caffrey
Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
FEBS Lett 499:6-10. 2001..We discuss the physiological significance of these studies in relation to recent work showing that dephosphorylation of Ins(1,3,4,5,6)P(5) to inositol 1,4,5,6-tetrakisphosphate is a cell signaling event... - Discovery of molecular and catalytic diversity among human diphosphoinositol-polyphosphate phosphohydrolases. An expanding Nudt familyJ J Caffrey
Inositide Signaling Group, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
J Biol Chem 275:12730-6. 2000..Thus, cells can recruit sophisticated molecular processes to regulate diphosphoinositol polyphosphate turnover... - myo-inositol 3,4,5,6-tetrakisphosphate inhibits an apical calcium-activated chloride conductance in polarized monolayers of a cystic fibrosis cell lineM A Carew
Inositide Signaling Section, Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
J Biol Chem 275:26906-13. 2000..These studies provide the first demonstration that, in a physiologically relevant context of a polarized monolayer, there is an apical, Ins(3,4,5,6)P(4)-inhibited CaCC... - Inositol 1,3,4-trisphosphate acts in vivo as a specific regulator of cellular signaling by inositol 3,4,5,6-tetrakisphosphateX Yang
Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
J Biol Chem 274:18973-80. 1999..7 microM), thereby suggesting a new strategy for the rational design of therapeutically useful kinase inhibitors. Overall, our data provide new information to support the idea that Ins(1,3,4)P3 acts in an important signaling cascade... - The transcriptional regulator, Arg82, is a hybrid kinase with both monophosphoinositol and diphosphoinositol polyphosphate synthase activityT Zhang
Inositide Signaling Section, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
FEBS Lett 494:208-12. 2001..We propose that Arg82 is an ancestral precursor of two distinct and specific enzyme families: inositol 1,4,5-trisphosphate kinases and diphosphoinositol polyphosphate synthases... - Regulation of a human chloride channel. a paradigm for integrating input from calcium, type ii calmodulin-dependent protein kinase, and inositol 3,4,5,6-tetrakisphosphateM W Ho
Inositide Signaling and Membrane Signaling Groups, Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
J Biol Chem 276:18673-80. 2001..These data provide a new context for understanding the physiological relevance of Ins(3,4,5,6)P(4) in the longer term regulation of Ca(2+)-dependent Cl(-) fluxes in epithelial cells... - Turnover of bis-diphosphoinositol tetrakisphosphate in a smooth muscle cell line is regulated by beta2-adrenergic receptors through a cAMP-mediated, A-kinase-independent mechanismS T Safrany
Inositide Signaling Group, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, PO Box 12233, NC 27709, USA
EMBO J 17:1710-6. 1998..Our results indicate a new signaling action of cAMP, and furnish an important focus for future research into the roles of diphosphorylated inositol phosphates in signal transduction... - The regulation of the phosphorylation of inositol 1,3,4-trisphosphate in cell-free preparations and its relevance to the formation of inositol 1,3,4,6-tetrakisphosphate in agonist-stimulated rat parotid acinar cellsP J Hughes
Inositol Lipid Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
J Biol Chem 264:19871-8. 1989..1-0.2 microM), which leads us to propose that inositol 3,4,5,6-tetrakisphosphate is an endogenous inhibitor of the kinase... - The human and rat forms of multiple inositol polyphosphate phosphatase: functional homology with a histidine acid phosphatase up-regulated during endochondral ossificationJ J Caffrey
Inositide Signaling Group, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA
FEBS Lett 442:99-104. 1999..The latter observation provides a context for proposing that MIPP may aid bone mineralization and salvage the inositol moiety prior to apoptosis... - HIV-1 envelope protein, gp120, has no effects on inositol phosphate production and metabolism in the Jurkat T-cell line either in the presence or absence of receptor stimulationM T Sumner
Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
FEBS Lett 413:75-80. 1997..This is the first report that biologically competent gp120 does not affect any aspect of inositol phosphate turnover in either basal or receptor-activated lymphocytes... - The importance to chondrocyte differentiation of changes in expression of the multiple inositol polyphosphate phosphataseKiyoshi Hidaka
Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, Kyushu University, Fukuoka 812 8582, Japan
Exp Cell Res 290:254-64. 2003..In any case, we conclude that Minpp is important to chondrocyte differentiation, but in a manner that is, surprisingly, independent of inositol polyphosphate turnover... - Multitasking in signal transduction by a promiscuous human Ins(3,4,5,6)P(4) 1-kinase/Ins(1,3,4)P(3) 5/6-kinaseX Yang
Inositide Signaling Section, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
Biochem J 351:551-5. 2000..1 microM; V(max)=780 pmol/min per microg) actively compete for phosphorylation in vivo. This competition empowers the kinase with multitasking capability in several key aspects of inositol phosphate signalling... - Molecular cloning and expression of a rat hepatic multiple inositol polyphosphate phosphataseA Craxton
Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
Biochem J 328:75-81. 1997..Biol. Chem. 268, 6161-6167]... - A novel context for the 'MutT' module, a guardian of cell integrity, in a diphosphoinositol polyphosphate phosphohydrolaseS T Safrany
Inositide Signaling Group, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, PO Box 12233, NC 27709, USA
EMBO J 17:6599-607. 1998..Because overlapping substrate specificity is a feature of this class of proteins, our data provide new directions for future studies of higher inositol phosphates... - Human immunodeficiency virus type 1 envelope protein does not stimulate either prostaglandin formation or the expression of prostaglandin H synthase in THP-1 human monocytes/macrophagesR Hui
Eicosanoid Biochemistry Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
J Virol 69:8020-6. 1995..These results indicate that activation of the CD4-p56lck receptor signal transduction pathway by the HIV envelope protein does not increase prostaglandin formation... - Hepatic Ins(1,3,4,5)P4 3-phosphatase is compartmentalized inside endoplasmic reticulumN Ali
Laboratory of Cellular and Molecular Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
J Biol Chem 268:6161-7. 1993..Thus, hepatic 3-phosphatase has a highly restricted access to inositol polyphosphates in vivo that needs to be accounted for in the determination of the physiological role of this enzyme... - Paralogous murine Nudt10 and Nudt11 genes have differential expression patterns but encode identical proteins that are physiologically competent diphosphoinositol polyphosphate phosphohydrolasesLen V Hua
Inositide Signaling Section, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
Biochem J 373:81-9. 2003..Thus the significance of the Nudt10/Nudt11 duplication is specific hydrolysis of diphosphoinositol polyphosphates in a tissue-dependent manner... - Signaling by higher inositol polyphosphates. Synthesis of bisdiphosphoinositol tetrakisphosphate ("InsP8") is selectively activated by hyperosmotic stressXavier Pesesse
Inositide Signaling Group, NIEHS, National Institutes of Health, Department of Health and Social Services, Research Triangle Park, North Carolina 27709, USA
J Biol Chem 279:43378-81. 2004..JNK did not participate in regulating [PP]2-InsP4 levels. Identification of [PP]2-InsP4 as a sensor of hyperosmotic stress opens up a new area of research for studies into the cellular activities of higher inositol phosphates... - Cellular energetic status supervises the synthesis of bis-diphosphoinositol tetrakisphosphate independently of AMP-activated protein kinaseKuicheon Choi
Inositide Signaling Group, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
Mol Pharmacol 74:527-36. 2008..We conclude that the levels and hence the signaling strength of [PP](2)-InsP(4) is supervised by cellular adenosine nucleotide balance, signifying a new link between signaling and bioenergetic networks... - Avian multiple inositol polyphosphate phosphatase is an active phytase that can be engineered to help ameliorate the planet's "phosphate crisis"Jaiesoon Cho
Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, NIH, DHSS, Research Triangle Park, PO Box 12233, NC 27709, USA
J Biotechnol 126:248-59. 2006..This version of the enzyme was actively secreted without affecting either cell viability or the cellular levels of any inositol phosphates. Our studies offer a genetic strategy for greatly improving dietary InsP6 digestion in poultry... - Apical localization of ITPK1 enhances its ability to be a modifier gene product in a murine tracheal cell model of cystic fibrosisLing Yang
Inositol Signaling Section, and N I E H S N I H D H S S, Research Triangle Park, NC 27709, USA
J Cell Sci 119:1320-8. 2006..Compartmentalization of Ins(3,4,5,6)P4 synthesis adjacent to its site of action will enhance its regulatory capacity... - An adjacent pair of human NUDT genes on chromosome X are preferentially expressed in testis and encode two new isoforms of diphosphoinositol polyphosphate phosphohydrolaseKiyoshi Hidaka
Inositide Signaling Section, Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
J Biol Chem 277:32730-8. 2002..The hDIPP3 pair add tissue-specific diversity to the molecular mechanisms regulating diphosphoinositol polyphosphate turnover... - The Ins(1,3,4)P3 5/6-kinase/Ins(3,4,5,6)P4 1-kinase is not a protein kinaseXun Qian
Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, NIH, DHSS, Research Triangle Park, PO Box 12233, NC 27709, USA
Biochem J 389:389-95. 2005..Cell 15, 689-701]... - Regulation of Ins(3,4,5,6)P(4) signaling by a reversible kinase/phosphataseMelisa W Y Ho
Inositide Signaling Group, Laboratory of Signal Transduction and National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
Curr Biol 12:477-82. 2002..Reciprocal coordination of these opposing reactions offers an alternative to general doctrine that intracellular signals are regulated by integrating multiple, distinct phosphatases and kinases... - Physiological levels of PTEN control the size of the cellular Ins(1,3,4,5,6)P(5) poolSandrine Deleu
Inositol Signaling Section, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, NIH, DHSS, Research Triangle Park, NC 27709, USA
Cell Signal 18:488-98. 2006..Huang, R.P. Wernyj, D.D. Norton, P. Precht, M.C. Seminario, R.L. Wange, Oncogene, 24 (2005) 3819 ] the levels of which are modulated by expression of the highly pleiotropic PTEN protein... - Purification, sequencing, and molecular identification of a mammalian PP-InsP5 kinase that is activated when cells are exposed to hyperosmotic stressJae H Choi
Inositide Signaling Group Laboratory of Signal Transduction, NIEHS, National Institutes of Health, DHHS, North Carolina 27709, USA
J Biol Chem 282:30763-75. 2007..2 M sorbitol; 30 min) revealed a persistent, 3.9 +/- 0.4-fold activation when compared with control cells. PPIP5Ks are likely to be important signaling enzymes... - Dephosphorylation of 2,3-bisphosphoglycerate by MIPP expands the regulatory capacity of the Rapoport-Luebering glycolytic shuntJaiesoon Cho
Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Social Services, P O Box 12233, Research Triangle Park, NC 27709, USA
Proc Natl Acad Sci U S A 105:5998-6003. 2008..4. This phenomenon provides a homeostatic mechanism for elevating 2,3-BPG levels, thereby enhancing oxygen release to tissues. Our data indicate greater biological significance of the Rapoport-Luebering shunt than previously considered... - An expanded biological repertoire for Ins(3,4,5,6)P4 through its modulation of ClC-3 functionJennifer Mitchell
Inositol Signaling Group, National Institute of Environmental Health Sciences, National Institutes of Health, U S Department of Health and Human Services, P O Box 12233, Research Triangle Park, North Carolina 27709, USA
Curr Biol 18:1600-5. 2008..Among other ClC-3 functions that could be regulated by Ins(3,4,5,6)P4 are tumor cell migration [7], apoptosis [8], and inflammatory responses [9]. Ins(3,4,5,6)P4 is a ubiquitous cellular signal with diverse biological actions... - Pathogenicity of Salmonella: SopE-mediated membrane ruffling is independent of inositol phosphate signalsSandrine Deleu
Inositol Signaling Section, National Institute of Environmental Health Sciences, NIH, DHSS, Research Triangle Park, NC 27709, USA
FEBS Lett 580:1709-15. 2006.... - Integration of inositol phosphate signaling pathways via human ITPK1Philip P Chamberlain
Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA
J Biol Chem 282:28117-25. 2007..Our work describes a novel mode of substrate regulation and provides insight into the enzyme evolution of a signaling mechanism from a metabolic role... - scyllo-inositol pentakisphosphate as an analogue of myo-inositol 1,3,4,5,6-pentakisphosphate: chemical synthesis, physicochemistry and biological applicationsAndrew M Riley
Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, UK
Chembiochem 7:1114-22. 2006..This finding both reinforces the value of scyllo-InsP(5) as a biological control and shows that the axial 2-OH group of Ins(1,3,4,5,6)P(5) plays a part in substrate recognition by PTEN and the Ins(1,3,4,5,6)P(5) 2-kinases... - On the contribution of stereochemistry to human ITPK1 specificity: Ins(1,4,5,6)P4 is not a physiologic substrateAndrew M Riley
Wolfson Laboratory for Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, UK
FEBS Lett 580:324-30. 2006..18 microM) by inositolphosphate-multikinase... - Inositol 3,4,5,6-tetrakisphosphate inhibits insulin granule acidification and fusogenic potentialErik Renstrom
Department of Physiological Sciences, Lund University, BMC F11 SE 221 84 Lund, Sweden
J Biol Chem 277:26717-20. 2002..This may impinge upon type 2 diabetes etiology. Regulatory control over vesicle acidification by this negative signaling pathway in other cell types should be considered... - Cytosolic multiple inositol polyphosphate phosphatase in the regulation of cytoplasmic free Ca2+ concentrationJia Yu
Department of Molecular Medicine, The Rolf Luft Center for Diabetes Research, L3, Karolinska Institutet, Karolinska Hospital, Stockholm SE-171 76, Sweden
J Biol Chem 278:46210-8. 2003.... - Cystic fibrosis airway epithelial Ca2+ i signaling: the mechanism for the larger agonist-mediated Ca2+ i signals in human cystic fibrosis airway epitheliaCarla M Pedrosa Ribeiro
Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, North Carolina 27599-7248, USA
J Biol Chem 280:10202-9. 2005..Greater ER-derived Ca(2+)(i) signals may provide a compensatory mechanism to restore, at least acutely, mucus clearance in CF airways... - In Saccharomyces cerevisiae, the inositol polyphosphate kinase activity of Kcs1p is required for resistance to salt stress, cell wall integrity, and vacuolar morphogenesisEvelyne Dubois
Institut de Recherches Microbiologiques Jean Marie Wiame, Universite Libre de Bruxelles, Brussels, Belgium B 1070
J Biol Chem 277:23755-63. 2002..Our results show that diphosphoinositol polyphosphate synthase activity is essential for biogenesis of the yeast vacuole and the cell's responses to certain environmental stresses... - Metabolic and signaling properties of an Itpk gene family in Glycine maxAmanda R Stiles
Department of Plant Pathology, Physiology and Weed Science, Virginia Polytechnic Institute and State University, 413 Price Hall, Blacksburg, VA 24061, USA
FEBS Lett 582:1853-8. 2008..The soybean Itpks also phosphorylated Ins(3,4,6)P3 to Ins(1,3,4,6)P4 which was further phosphorylated to Ins(1,3,4,5,6)P5 by soybean Ipk2. Thus, soybean Itpks may participate in an inositol lipid-independent pathway of InsP6 synthesis...