SHP-2

Summary

Gene Symbol: SHP-2
Description: protein tyrosine phosphatase, non-receptor type 11
Alias: BPTP3, CFC, JMML, METCDS, NS1, PTP-1D, PTP2C, SH-PTP2, SH-PTP3, SHP2, tyrosine-protein phosphatase non-receptor type 11, PTP-2C, protein-tyrosine phosphatase 1D, protein-tyrosine phosphatase 2C
Species: human

Top Publications

  1. pmc Functional effects of PTPN11 (SHP2) mutations causing LEOPARD syndrome on epidermal growth factor-induced phosphoinositide 3-kinase/AKT/glycogen synthase kinase 3beta signaling
    Thomas Edouard
    INSERM U563, Centre de Physiopathologie de Toulouse Purpan, BP3028, Toulouse, F 31024, France
    Mol Cell Biol 30:2498-507. 2010
  2. pmc Development of severe skeletal defects in induced SHP-2-deficient adult mice: a model of skeletal malformation in humans with SHP-2 mutations
    Timothy J Bauler
    Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109 5620, USA
    Dis Model Mech 4:228-39. 2011
  3. pmc The tyrosine phosphatase SHP2 regulates recovery of endothelial adherens junctions through control of β-catenin phosphorylation
    Ilse Timmerman
    Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, The Netherlands
    Mol Biol Cell 23:4212-25. 2012
  4. pmc Structural and mechanistic insights into LEOPARD syndrome-associated SHP2 mutations
    Zhi Hong Yu
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    J Biol Chem 288:10472-82. 2013
  5. ncbi SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein
    Hideaki Higashi
    Division of Molecular Oncology, Institute for Genetic Medicine and Graduate School of Science, Hokkaido University, Sapporo 060 0815, Japan
    Science 295:683-6. 2002
  6. pmc LST1/A is a myeloid leukocyte-specific transmembrane adaptor protein recruiting protein tyrosine phosphatases SHP-1 and SHP-2 to the plasma membrane
    Peter Dráber
    Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 142 20 Prague, Czech Republic
    J Biol Chem 287:22812-21. 2012
  7. doi Tyrosine phosphatases as key regulators of StAR induction and cholesterol transport: SHP2 as a potential tyrosine phosphatase involved in steroid synthesis
    Mariana Cooke
    Department of Biochemistry IIMHNO, School of Medicine, University of Buenos Aires, Paraguay 2155, 5th, C1121ABG Buenos Aires, Argentina
    Mol Cell Endocrinol 336:63-9. 2011
  8. pmc Genetic factors associated with intestinal metaplasia in a high risk Singapore-Chinese population: a cohort study
    Feng Zhu
    Department of Medicine, National University of Singapore, Singapore, Singapore
    BMC Gastroenterol 9:76. 2009
  9. doi Calpain-dependent cleavage of SHP-1 and SHP-2 is involved in the dephosphorylation of Jurkat T cells induced by Entamoeba histolytica
    K A Kim
    Department of Environmental Medical Biology, Institute of Tropical Medicine, and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
    Parasite Immunol 32:176-83. 2010
  10. ncbi Germ-line and somatic PTPN11 mutations in human disease
    Marco Tartaglia
    Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanita, Viale Regina Elena, 299, 00161 Rome, Italy
    Eur J Med Genet 48:81-96. 2005

Research Grants

  1. Cardiofaciocutaneous Syndrome & Noonan Syndrome Meeting
    Amy Roberts; Fiscal Year: 2006
  2. Shyam S Mohapatra; Fiscal Year: 2015
  3. Zhong Yin Zhang; Fiscal Year: 2016
  4. MARIA IRENE KONTARIDIS; Fiscal Year: 2016
  5. Molecular Pathogenesis of the Cardiomyogenic Defects in LEOPARD Syndrome
    MARIA IRENE KONTARIDIS; Fiscal Year: 2010
  6. STRUCTURES OF RNA BINDING PROTEINS FROM INFLUENZA VIRUS
    Gaetano Montelione; Fiscal Year: 2000
  7. Zhong Yin Zhang; Fiscal Year: 2014
  8. Role of PTPN11 Mutations in Myeloid Leukemogenesis
    Kevin M Shannon; Fiscal Year: 2010
  9. MMDx: A rapid multiplexed matrix code diagnostic for real time epidemiology
    Lee Gehrke; Fiscal Year: 2013
  10. Dengue diagnostics using a novel peroxidase chain reaction (PxCR)
    PETER PETER ZASSENHAUS; Fiscal Year: 2013

Detail Information

Publications301 found, 100 shown here

  1. pmc Functional effects of PTPN11 (SHP2) mutations causing LEOPARD syndrome on epidermal growth factor-induced phosphoinositide 3-kinase/AKT/glycogen synthase kinase 3beta signaling
    Thomas Edouard
    INSERM U563, Centre de Physiopathologie de Toulouse Purpan, BP3028, Toulouse, F 31024, France
    Mol Cell Biol 30:2498-507. 2010
    ..developmental abnormalities, is mainly due to mutations that impair the activity of the tyrosine phosphatase SHP2 (PTPN11). How these alterations cause the disease remains unknown...
  2. pmc Development of severe skeletal defects in induced SHP-2-deficient adult mice: a model of skeletal malformation in humans with SHP-2 mutations
    Timothy J Bauler
    Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109 5620, USA
    Dis Model Mech 4:228-39. 2011
    ....
  3. pmc The tyrosine phosphatase SHP2 regulates recovery of endothelial adherens junctions through control of β-catenin phosphorylation
    Ilse Timmerman
    Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, The Netherlands
    Mol Biol Cell 23:4212-25. 2012
    ..mediator thrombin, we demonstrate an important role for the Src homology 2-domain containing tyrosine phosphatase (SHP2) in mediating recovery of the VE-cadherin-controlled endothelial barrier...
  4. pmc Structural and mechanistic insights into LEOPARD syndrome-associated SHP2 mutations
    Zhi Hong Yu
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    J Biol Chem 288:10472-82. 2013
    b>SHP2 is an allosteric phosphatase essential for growth factor-mediated Ras activation...
  5. ncbi SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein
    Hideaki Higashi
    Division of Molecular Oncology, Institute for Genetic Medicine and Graduate School of Science, Hokkaido University, Sapporo 060 0815, Japan
    Science 295:683-6. 2002
    ..Conversely, the CagA effect on cells was reproduced by constitutively active SHP-2. Thus, upon translocation, CagA perturbs cellular functions by deregulating SHP-2...
  6. pmc LST1/A is a myeloid leukocyte-specific transmembrane adaptor protein recruiting protein tyrosine phosphatases SHP-1 and SHP-2 to the plasma membrane
    Peter Dráber
    Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 142 20 Prague, Czech Republic
    J Biol Chem 287:22812-21. 2012
    ..In addition, it binds SHP-1 and SHP-2 phosphatases in a phosphotyrosine-dependent manner, facilitating their recruitment to the plasma membrane. These data suggest a role for LST1/A in negative regulation of signal propagation...
  7. doi Tyrosine phosphatases as key regulators of StAR induction and cholesterol transport: SHP2 as a potential tyrosine phosphatase involved in steroid synthesis
    Mariana Cooke
    Department of Biochemistry IIMHNO, School of Medicine, University of Buenos Aires, Paraguay 2155, 5th, C1121ABG Buenos Aires, Argentina
    Mol Cell Endocrinol 336:63-9. 2011
    ..Here, we will describe the role of protein tyrosine phosphatases in the regulation of steroid biosynthesis, relating them to steroidogenic acute regulatory protein, arachidonic acid metabolism and mitochondrial rearrangement...
  8. pmc Genetic factors associated with intestinal metaplasia in a high risk Singapore-Chinese population: a cohort study
    Feng Zhu
    Department of Medicine, National University of Singapore, Singapore, Singapore
    BMC Gastroenterol 9:76. 2009
    ..A total of 18 polymorphisms in 14 candidate genes were evaluated in a Singapore-Chinese population at high risk of developing GC...
  9. doi Calpain-dependent cleavage of SHP-1 and SHP-2 is involved in the dephosphorylation of Jurkat T cells induced by Entamoeba histolytica
    K A Kim
    Department of Environmental Medical Biology, Institute of Tropical Medicine, and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
    Parasite Immunol 32:176-83. 2010
    ..These results suggest that calpain-dependent cleavage of SHP-1 and SHP-2 may contribute to protein tyrosine dephosphorylation in Jurkat T cell death induced by E. histolytica...
  10. ncbi Germ-line and somatic PTPN11 mutations in human disease
    Marco Tartaglia
    Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanita, Viale Regina Elena, 299, 00161 Rome, Italy
    Eur J Med Genet 48:81-96. 2005
    ..This review focuses on the role of SHP-2 in signal transduction, development and hematopoiesis, as well as on the consequences of SHP-2 gain-of-function...
  11. ncbi Genetic evidence for lineage-related and differentiation stage-related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia
    Marco Tartaglia
    Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanita, Viale Regina Elena, 299 00161 Rome, Italy
    Blood 104:307-13. 2004
    ..Our findings provide evidence for a wider role of PTPN11 lesions in leukemogenesis, but also suggest a lineage-related and differentiation stage-related contribution of these lesions to clonal expansion...
  12. ncbi BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1
    Norihiko Watanabe
    Department of Pathology and Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, Box 8118, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
    Nat Immunol 4:670-9. 2003
    ..B7x, a peripheral homolog of B7, is a ligand of BTLA. Thus, BTLA is a third inhibitory receptor on T lymphocytes with similarities to cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1)...
  13. ncbi Distinct interactions of the X-linked lymphoproliferative syndrome gene product SAP with cytoplasmic domains of members of the CD2 receptor family
    J Lewis
    Metabolism Branch, National Cancer Institute, Bethesda, Maryland 20892 1578, USA
    Clin Immunol 100:15-23. 2001
    ....
  14. pmc Concerted activity of tyrosine phosphatase SHP-2 and focal adhesion kinase in regulation of cell motility
    S Manes
    Department of Immunology and Oncology, Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid, Campus de Cantoblanco, E 28049 Madrid, Spain
    Mol Cell Biol 19:3125-35. 1999
    ..Abrogation of SHP-2 catalytic activity with a dominant-negative mutant (SHP2-C>S) abolishes IGF-I-induced FAK dephosphorylation, and cells expressing SHP2-C>S show reduced IGF-I-..
  15. ncbi The Protein-tyrosine-phosphatase SHP2 is phosphorylated on serine residues 576 and 591 by protein kinase C isoforms alpha, beta 1, beta 2, and eta
    Volker Strack
    Medical Clinic, Department IV, Eberhard Karls University Tubingen, Otfried Muller Strasse 10, D 72076 Tubingen, Germany
    Biochemistry 41:603-8. 2002
    ..pathway, we co-overexpressed PKC isoforms together with insulin receptor, docking proteins, and the PTPs SHP1 and SHP2 in human embryonic kidney (HEK) 293 cells...
  16. doi Isolation of a distinct class of gain-of-function SHP-2 mutants with oncogenic RAS-like transforming activity from solid tumors
    D Miyamoto
    Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan
    Oncogene 27:3508-15. 2008
    ..Although rare in solid tumors, the identified T507K SHP-2 represents a distinct class of SHP-2 mutants with oncogenic RAS-like transforming activity, which could contribute to the development of solid tumors...
  17. doi Phenotypic spectrum of 80 Greek patients referred as Noonan syndrome and PTPN11 mutation analysis: the value of initial clinical assessment
    Anna Papadopoulou
    3rd Department of Pediatrics, University General Hospital Attikon, University of Athens, Athens, Greece
    Eur J Pediatr 171:51-8. 2012
    ....
  18. pmc CD300a and CD300f differentially regulate the MyD88 and TRIF-mediated TLR signalling pathways through activation of SHP-1 and/or SHP-2 in human monocytic cell lines
    Eun Ju Kim
    School of Life Sciences and Biotechnology, Kyungpook National University, Daegu, Department of Pharmacology, Brain Science and Engineering Institute, School of Medicine, Kyungpook National University, Daegu, Korea
    Immunology 135:226-35. 2012
    ..These data indicate that CD300a and CD300f regulate the MyD88 and TRIF-mediated TLR signalling pathways through differential activation of SHP-1 and SHP-2...
  19. doi Helicobacter pylori-related host gene polymorphisms associated with susceptibility of gastric carcinogenesis: a two-stage case-control study in Chinese
    Caiyun He
    Department of Tumor Etiology and Screening, Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Tumor Etiology and Prevention in Liaoning Province, Shenyang 110001, China
    Carcinogenesis 34:1450-7. 2013
    ..pylori, were associated with the risks of GC and/or GA that precede carcinoma. Functional studies and further independent large-scale studies especially in other ethnic populations are still needed to confirm our results. ..
  20. pmc Polymorphisms of PTPN11 gene could influence serum lipid levels in a sex-specific pattern
    Zhi Fang Jia
    Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun 130021, China
    Lipids Health Dis 12:72. 2013
    ..The aim of this study was to explore the relationship between single nucleotide polymorphisms (SNPs) of PTPN11 and serum lipids in Northeast Chinese...
  21. pmc PTPN11-associated mutations in the heart: has LEOPARD changed Its RASpots?
    Jessica Lauriol
    Department of Medicine, Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
    Trends Cardiovasc Med 21:97-104. 2011
    ..mutations in the PTPN11 gene, encoding the Src homology-2 (SH2) domain-containing protein tyrosine phosphatase SHP2. PTPN11 mutations cause LEOPARD syndrome (LS) and Noonan syndrome (NS), two disorders that are part of a newly ..
  22. doi Overexpression of protein phosphatase non-receptor type 11 (PTPN11) in gastric carcinomas
    Jin Soo Kim
    Department of Internal Medicine, College of Medicine, Uijongbu St Mary s Hospital, The Catholic University of Korea, Seoul, Korea
    Dig Dis Sci 55:1565-9. 2010
    ..Protein phosphatase non-receptor type 11 (PTPN11) is a positive signaling PTP that activates RAS and ERK signaling. Also, the PTPN11 binds with CagA of Helicobacter pylori in gastric epithelial cells...
  23. pmc Cancer risk in patients with Noonan syndrome carrying a PTPN11 mutation
    Marjolijn C J Jongmans
    Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
    Eur J Hum Genet 19:870-4. 2011
    ..In conclusion, this study provides first evidence of an increased risk of cancer in patients with NS and a PTPN11 mutation, compared with that in the general population. Our data do not warrant specific cancer surveillance...
  24. pmc mSiglec-E, a novel mouse CD33-related siglec (sialic acid-binding immunoglobulin-like lectin) that recruits Src homology 2 (SH2)-domain-containing protein tyrosine phosphatases SHP-1 and SHP-2
    Z Yu
    Pharmaceutical Sector, Biotechnology Research Institute, National Research Council of Canada, Montreal, Quebec, Canada H4P 2R2
    Biochem J 353:483-92. 2001
    ..The gene encoding mSiglec-E is localized in the same chromosome as that encoding mouse CD33. Phylogenetic analysis reveals that neither mouse mSiglec-E nor CD33 shows a clear relationship with any human siglecs so far identified...
  25. ncbi Differential signaling by the epidermal growth factor-like growth factors neuregulin-1 and neuregulin-2
    C S Crovello
    Division of Signal Transduction, Beth Israel Deaconess Medical Center and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 273:26954-61. 1998
    ..the EGF receptor, stimulating receptor tyrosine phosphorylation and the recruitment of phospholipase C-gamma, Cbl, SHP2, and Shc to that receptor...
  26. ncbi PILRalpha, a novel immunoreceptor tyrosine-based inhibitory motif-bearing protein, recruits SHP-1 upon tyrosine phosphorylation and is paired with the truncated counterpart PILRbeta
    D D Mousseau
    Mammalian Cell Genetics, National Research Council Biotechnology Research Institute, Montreal, Quebec H4P 2R2
    J Biol Chem 275:4467-74. 2000
    ..The PILRalpha and PILRbeta genes are localized to chromosome 7 which is in contrast with the mapping of known members of the inhibitory receptor superfamily...
  27. pmc Negative regulation of Ros receptor tyrosine kinase signaling. An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1
    H Keilhack
    Research Unit, Molecular Cell Biology, D 07747 Jena, Germany
    J Cell Biol 152:325-34. 2001
    ..Overexpression of SHP-1 results in Ros dephosphorylation and effectively downregulates Ros-dependent proliferation and transformation. We propose that SHP-1 is an important downstream regulator of Ros signaling...
  28. ncbi Roles of the complex formation of SHPS-1 with SHP-2 in insulin-stimulated mitogen-activated protein kinase activation
    T Takada
    Second Department of Internal Medicine, Kobe University School of Medicine, Kusunoki cho, Chuo Ku, Kobe 650, Japan
    J Biol Chem 273:9234-42. 1998
    ....
  29. pmc SHP-2 phosphatase activity is required for PECAM-1-dependent cell motility
    Jing Xu Zhu
    Pulmonary, Allergy and Critical Care Division, SVM Hill Pavilion, Rm 410B, 380 South Univ Ave, Philadelphia, PA 19104 4539, USA
    Am J Physiol Cell Physiol 299:C854-65. 2010
    ....
  30. ncbi PD-L2 is a second ligand for PD-1 and inhibits T cell activation
    Y Latchman
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Nat Immunol 2:261-8. 2001
    ..Taken together, these studies show overlapping functions of PD-L1 and PD-L2 and indicate a key role for the PD-L-PD-1 pathway in regulatingT cell responses...
  31. ncbi A family of proteins that inhibit signalling through tyrosine kinase receptors
    A Kharitonenkov
    Department of Molecular Biology, Max Planck Institute für Biochemie, Martinsried, Germany
    Nature 386:181-6. 1997
    ..Our findings indicate that proteins belonging to the SIRP family generally regulate signals defining different physiological and pathological processes...
  32. pmc Structure and function of Cas-L, a 105-kD Crk-associated substrate-related protein that is involved in beta 1 integrin-mediated signaling in lymphocytes
    M Minegishi
    Dana Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Exp Med 184:1365-75. 1996
    ..Furthermore, we demonstrate that integrin/ligand binding results in the recruitment of Crk, Nck, and SHPTP2 to pp105. These findings further define the roles of pp105/Cas-L and pp125FAK in the integrin-mediated signaling pathways...
  33. ncbi Molecular cloning of MIS, a myeloid inhibitory siglec, that binds protein-tyrosine phosphatases SHP-1 and SHP-2
    T Ulyanova
    Howard Hughes Medical Institute, Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 276:14451-8. 2001
    ..Moreover, MIS exerted an inhibitory effect on FcgammaRI receptor-induced calcium mobilization. These data suggest that MIS can play an inhibitory role through its ITIM sequences...
  34. pmc Identification of a human src homology 2-containing protein-tyrosine-phosphatase: a putative homolog of Drosophila corkscrew
    R M Freeman
    Committee on Virology, Harvard University, Boston, MA 02115
    Proc Natl Acad Sci U S A 89:11239-43. 1992
    ....
  35. pmc PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity
    Marco Tartaglia
    Department of Pediatrics, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA
    Am J Hum Genet 70:1555-63. 2002
    ..A PTPN11 mutation was identified in a family inheriting Noonan-like/multiple giant-cell lesion syndrome, extending the phenotypic range of disease associated with this gene...
  36. pmc A widely expressed human protein-tyrosine phosphatase containing src homology 2 domains
    S Ahmad
    Biotechnology Research Institute, National Research Council of Canada, Montreal, PQ
    Proc Natl Acad Sci U S A 90:2197-201. 1993
    A cDNA encoding a nontransmembrane protein-tyrosine phosphatase (PTP; EC 3.1.3.48), termed PTP2C, was isolated from a human umbilical cord cDNA library...
  37. ncbi Regulation of T cell receptor signaling by tyrosine phosphatase SYP association with CTLA-4
    L E Marengere
    Amgen Institute, Toronto, Ontario, Canada
    Science 272:1170-3. 1996
    ..The CTLA-4-associated SYP had phosphatase activity toward the RAS regulator p52SHC. Thus, the RAS pathway and T cell activation through the T cell receptor are regulated by CTLA-4-associated SYP...
  38. ncbi The CagA protein of Helicobacter pylori is translocated into epithelial cells and binds to SHP-2 in human gastric mucosa
    Shiho Yamazaki
    Second Department of Internal Medicine, Fukui Medical University, Japan
    J Infect Dis 187:334-7. 2003
    ..Deregulation of SHP-2 by CagA may play a role in the acquisition of a cellular-transformed phenotype at a relatively early stage of multistep gastric carcinogenesis...
  39. doi Hodgkin's lymphoma in a patient with Noonan syndrome with germ-line PTPN11 mutations
    Fu Sung Lo
    Department of Pediatrics, Chang Gung Memorial Hospital, Chung Gung University College of Medicine, Taoyuan, Taiwan
    Int J Hematol 88:287-90. 2008
    ..This somatic mutation has ever been reported in juvenile myelomonocytic leukemia (JMML). Furthermore, the functional analysis of this mutant SHP-2 has shown it to have enhanced phosphatase activity...
  40. ncbi SHP2 association with VE-cadherin complexes in human endothelial cells is regulated by thrombin
    J A Ukropec
    Department of Physiology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 6799, USA
    J Biol Chem 275:5983-6. 2000
    ..We demonstrate that the nonreceptor protein-tyrosine phosphatase SHP2 co-precipitates with VE-cadherin complexes in confluent, quiescent human umbilical vein endothelial cells...
  41. ncbi Inhibition of antigen-induced T cell response and antibody-induced NK cell cytotoxicity by NKG2A: association of NKG2A with SHP-1 and SHP-2 protein-tyrosine phosphatases
    E Le Dréan
    INSERM U463, Institut de Biologie et Faculté des Sciences, Nantes, France
    Eur J Immunol 28:264-76. 1998
    ..Our results suggest that this inhibitory pathway sets the threshold of T and NK cell activation...
  42. ncbi Requirement for protein-tyrosine phosphatase SHP-2 in insulin-induced activation of c-Jun NH(2)-terminal kinase
    K Fukunaga
    Second Department of Internal Medicine, Kobe University School of Medicine, 7 5 1 Kusunoki cho, Chuo Ku, Kobe 650 0017, Japan
    J Biol Chem 275:5208-13. 2000
    ..These results suggest that SHP-2 contributes to JNK activation in response to insulin by positively regulating the Ras signaling pathway at the same level as, or upstream from, SOS...
  43. ncbi Cutting edge: TREM-like transcript-1, a platelet immunoreceptor tyrosine-based inhibition motif encoding costimulatory immunoreceptor that enhances, rather than inhibits, calcium signaling via SHP-2
    Alexander D Barrow
    Cambridge Institute for Medical Research, Wellcome Trust, Addenbrookes Hospital, Cambridge, United Kingdom
    J Immunol 172:5838-42. 2004
    ..Therefore, TLT1 represents a new costimulatory ITIM immunoreceptor and is the second ITIM-bearing receptor to be identified in platelets after platelet endothelial cell adhesion molecule-1...
  44. ncbi Pathways downstream of Shc and Grb2 are required for cell transformation by the tpr-Met oncoprotein
    E D Fixman
    Molecular Oncology Group, Royal Victoria Hospital, Department of Medicine, McGill University, Montreal, Quebec, H3A 1A1 Canada
    J Biol Chem 271:13116-22. 1996
    ....
  45. pmc A novel membrane glycoprotein, SHPS-1, that binds the SH2-domain-containing protein tyrosine phosphatase SHP-2 in response to mitogens and cell adhesion
    Y Fujioka
    Second Department of Internal Medicine, Kobe University School of Medicine, Chuo Ku, Japan
    Mol Cell Biol 16:6887-99. 1996
    ..In addition, we suggest that SHPS-1 may be a potential substrate for SHP-2 and may function in both growth factor- and cell adhesion-induced cell signaling...
  46. ncbi Platelet endothelial cell adhesion molecule-1 is a major SH-PTP2 binding protein in vascular endothelial cells
    M Masuda
    Department of Structural Analysis, National Cardiovascular Center Research Institute, Suita, Osaka, Japan
    FEBS Lett 408:331-6. 1997
    ..the c-Src phosphorylated PECAM-1 cytoplasmic domain and was identified as a protein tyrosine phosphatase SH-PTP2 (SHP2, Syp)...
  47. pmc SHP-1 binds and negatively modulates the c-Kit receptor by interaction with tyrosine 569 in the c-Kit juxtamembrane domain
    M Kozlowski
    Health Canada Life Sciences and the University of Ottawa, Canada
    Mol Cell Biol 18:2089-99. 1998
    ....
  48. ncbi Tyrosine 1213 of Flt-1 is a major binding site of Nck and SHP-2
    K Igarashi
    Life Science Research Center, Nippon Steel Corporation, Kawasaki, Japan
    Biochem Biophys Res Commun 246:95-9. 1998
    ..Nck also binds to Y1333 of Flt-1. These results suggest that Nck, SHP-2, PLC gamma, and PI3K play important roles in Flt-1 signal transduction and that Y1213 of Flt-1 is a major binding site of PI3K, Nck, and SHP-2...
  49. ncbi The COOH-terminal tyrosine phosphorylation sites on IRS-1 bind SHP-2 and negatively regulate insulin signaling
    M G Myers
    Research Division, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 273:26908-14. 1998
    ..These results suggest that SHP-2 attentuates the phosphorylation and downstream signal transmission of IRS-1 and that the interaction of IRS-1 and SHP-2 is an important regulatory event which attenuates insulin metabolic responses...
  50. ncbi Recruitment and activation of SHP-1 protein-tyrosine phosphatase by human platelet endothelial cell adhesion molecule-1 (PECAM-1). Identification of immunoreceptor tyrosine-based inhibitory motif-like binding motifs and substrates
    C T Hua
    Division of Human Immunology, Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide, South Australia, 5000 Australia
    J Biol Chem 273:28332-40. 1998
    ....
  51. ncbi The carboxyl-terminal region of biliary glycoprotein controls its tyrosine phosphorylation and association with protein-tyrosine phosphatases SHP-1 and SHP-2 in epithelial cells
    M Huber
    McGill Cancer Centre, Medicine, and Oncology, McGill University, Montreal, Quebec H3G 1Y6, Canada
    J Biol Chem 274:335-44. 1999
    ..Together, these results indicate that both SHP-1 and SHP-2 interact with the Bgp1 cytoplasmic domain via ITIM-like sequences. Furthermore, they reveal that the C-terminal amino acids of Bgp1 are critical for these interactions...
  52. ncbi Differential association of cytoplasmic signalling molecules SHP-1, SHP-2, SHIP and phospholipase C-gamma1 with PECAM-1/CD31
    N J Pumphrey
    Division of Immunity and Infection, University of Birmingham, UK
    FEBS Lett 450:77-83. 1999
    ....
  53. ncbi G6b, a novel immunoglobulin superfamily member encoded in the human major histocompatibility complex, interacts with SHP-1 and SHP-2
    E C de Vet
    Medical Research Council United Kingdom Human Genome Mapping Project Resource Center, Hinxton, Cambridge CB10 1SB, United Kingdom
    J Biol Chem 276:42070-6. 2001
    ..Mutagenesis studies showed that phosphorylation of tyrosine 211 is critical for the interaction of G6b with SHP-1 and SHP-2...
  54. ncbi Death receptors bind SHP-1 and block cytokine-induced anti-apoptotic signaling in neutrophils
    Isabelle Daigle
    Swiss Institute of Allergy and Asthma Research SIAF, Davos, Switzerland
    Nat Med 8:61-7. 2002
    ..Thus, we provide molecular and functional evidence for negative signaling by death receptors...
  55. ncbi Cloning and characterization of human Siglec-11. A recently evolved signaling molecule that can interact with SHP-1 and SHP-2 and is expressed by tissue macrophages, including brain microglia
    Takashi Angata
    Glycobiology Research and Training Center, Department of Medicine, University of California, San Diego, La Jolla, California 92093 0687, USA
    J Biol Chem 277:24466-74. 2002
    ....
  56. ncbi Some protein tyrosine phosphatases target in part to lipid rafts and interact with caveolin-1
    A Caselli
    Department of Biochemical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy
    Biochem Biophys Res Commun 296:692-7. 2002
    ..Collectively, our findings propose that particular PTPs could perform some of their cellular actions or are regulated by recruitment into caveolin-enriched membrane fractions...
  57. ncbi Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia
    Marco Tartaglia
    Department of Pediatrics, Mount Sinai School of Medicine, New York, New York, USA
    Nat Genet 34:148-50. 2003
    We report here that individuals with Noonan syndrome and juvenile myelomonocytic leukemia (JMML) have germline mutations in PTPN11 and that somatic mutations in PTPN11 account for 34% of non-syndromic JMML...
  58. ncbi SHP-2 regulates SOCS-1-mediated Janus kinase-2 ubiquitination/degradation downstream of the prolactin receptor
    Samir Ali
    Department of Medicine, Division of Hematology and Molecular Oncology Group, Royal Victoria Hospital, McGill University, Montreal, Quebec H3A 1A1, Canada
    J Biol Chem 278:52021-31. 2003
    ..Together our results provide a novel function for SHP-2 as a positive regulator of cytokine receptor signaling by regulating ubiquitination/degradation pathways...
  59. pmc Focal adhesion kinase is a substrate and downstream effector of SHP-2 complexed with Helicobacter pylori CagA
    Ryouhei Tsutsumi
    Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University, Kita 15, Nishi 7, Sapporo 060 0815, Japan
    Mol Cell Biol 26:261-76. 2006
    ..Impaired cell adhesion and increased motility by CagA may be involved in the development of gastric lesions associated with cagA-positive H. pylori infection...
  60. pmc Antagonism or synergism. Role of tyrosine phosphatases SHP-1 and SHP-2 in growth factor signaling
    Ning Wang
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Biol Chem 281:21878-83. 2006
    ..The interaction of SHP-1 and SHP-2 may be responsible for previously unexpected novel regulatory mechanism of cell signaling by tyrosine phosphatases...
  61. ncbi FcRL6, a new ITIM-bearing receptor on cytolytic cells, is broadly expressed by lymphocytes following HIV-1 infection
    Timothy J Wilson
    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA
    Blood 109:3786-93. 2007
    ....
  62. ncbi Oxidation sensitivity of the catalytic cysteine of the protein-tyrosine phosphatases SHP-1 and SHP-2
    Irene Weibrecht
    Department of Genetics and Pathology, Rudbeck Laboratory, University of Uppsala, SE 75185 Uppsala, Sweden
    Free Radic Biol Med 43:100-10. 2007
    ..The modulating effects of SH2 domains for oxidation of these PTPs are in support of an enhanced oxidation susceptibility of activated SHPs...
  63. ncbi Associations between a PTPN11 polymorphism and gastric atrophy--opposite in Uzbekistan to that in Japan
    Nobuyuki Hamajima
    Department of Preventive Medicine Medical Decision Making, Nagoya University Graduate School of Medicine, 65 Tsurumai Cho, Showa Ku, Nagoya, 466 8550 Japan
    Asian Pac J Cancer Prev 9:217-20. 2008
    ..18 (95% confidence interval, 0.04-0.86) for intron 3 GG genotype relative to AA genotype. Since the finding was opposite to that among Japanese, the H. pylori strains and/or lifestyle in Uzbekistan might modify the association...
  64. doi Downregulation of platelet responsiveness upon contact with LDL by the protein-tyrosine phosphatases SHP-1 and SHP-2
    Suzanne J A Korporaal
    Department of Clinical Chemistry and Haematology, University Medical Center, Utrecht, The Netherlands
    Arterioscler Thromb Vasc Biol 29:372-9. 2009
    ..We report a second mechanism that halts LDL signaling and in addition lowers platelet responsiveness to aggregating agents...
  65. ncbi Activation of the SH2-containing protein tyrosine phosphatase, SH-PTP2, by phosphotyrosine-containing peptides derived from insulin receptor substrate-1
    S Sugimoto
    Department of Biological Chemistry and Molecular Pharmacology, Beth Israel Hospital, Boston, Massachusetts 02115
    J Biol Chem 269:13614-22. 1994
    ..These data suggest that multiple levels for control of SH-PTP2 enzymatic activity may exist in vitro and in vivo...
  66. pmc The 64-kDa protein that associates with the platelet-derived growth factor receptor beta subunit via Tyr-1009 is the SH2-containing phosphotyrosine phosphatase Syp
    A Kazlauskas
    National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206
    Proc Natl Acad Sci U S A 90:6939-43. 1993
    ..These data raise the interesting possibility that protein-tyrosine phosphatases contribute to the intracellular relay of biological signals originating from receptor tyrosine kinases such as the PDGFR...
  67. ncbi Characterization of two SHP-2-associated binding proteins and potential substrates in hematopoietic cells
    H Gu
    Cancer Biology Program, Division of Hematology Oncology, Department of Medicine, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 272:16421-30. 1997
    ..Our results indicate that SHP-2 forms at least two separate complexes in hematopoietic cells and point to new potential SHP-2 targets...
  68. ncbi Transient association of the phosphotyrosine phosphatase SHP-2 with TrkA is induced by nerve growth factor
    B A Goldsmith
    Nervous System Group, Takarazuka Research Institute, Novartis Pharma K K, Takarazuka, Japan
    J Neurochem 69:1014-9. 1997
    ..We conclude that SHP-2 plays a significant role in early biochemical events in TrkA-mediated signal transduction...
  69. ncbi Interleukin-3 induces association of the protein-tyrosine phosphatase SHP2 and phosphatidylinositol 3-kinase with a 100-kDa tyrosine-phosphorylated protein in hemopoietic cells
    B L Craddock
    Pharmacology Group, Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, United Kingdom
    J Biol Chem 272:29281-9. 1997
    ..We have observed previously the co-immunoprecipitation of the p85 subunit of phosphatidylinositol-3 kinase (PI3K) and SHP2 in murine lymphohemopoietic cells after stimulation with interleukin-3...
  70. pmc Binding of Shp2 tyrosine phosphatase to FRS2 is essential for fibroblast growth factor-induced PC12 cell differentiation
    Y R Hadari
    Department of Pharmacology, New York University Medical Center, New York, New York 10016, USA
    Mol Cell Biol 18:3966-73. 1998
    ..report, we demonstrate that FRS2 forms a complex with the N-terminal SH2 domain of the protein tyrosine phosphatase Shp2 in response to FGF stimulation...
  71. ncbi Gab2, a new pleckstrin homology domain-containing adapter protein, acts to uncouple signaling from ERK kinase to Elk-1
    C Zhao
    Department of Biochemistry and Molecular Biology, and Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202 5254, USA
    J Biol Chem 274:19649-54. 1999
    ..Upon tyrosine phosphorylation, Gab2 physically interacts with Shp2 tyrosine phosphatase and Grb2 adapter protein...
  72. ncbi A critical role for phosphoinositide 3-kinase upstream of Gab1 and SHP2 in the activation of ras and mitogen-activated protein kinases by epidermal growth factor
    A Yart
    INSERM U326, IFR 30, Hopital Purpan, Toulouse 31059, INSERM U363, Hopital Cochin, 27 rue du Faubourg Saint Jacques, Paris 75014, France
    J Biol Chem 276:8856-64. 2001
    ..conventional effectors was independent of PI3K, we have observed that the recruitment of the tyrosine phosphatase SHP2 required PI3K...
  73. pmc Structural basis for the interaction of the free SH2 domain EAT-2 with SLAM receptors in hematopoietic cells
    M Morra
    Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    EMBO J 20:5840-52. 2001
    ..We conclude that EAT-2 plays a role in controlling signal transduction through at least four receptors expressed on the surface of professional antigen-presenting cells...
  74. pmc Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites
    Hideaki Higashi
    Division of Molecular Oncology, Institute for Genetic Medicine, Graduate School of Science, Hokkaido University, Sapporo 060 0815, Japan
    Proc Natl Acad Sci U S A 99:14428-33. 2002
    ..The presence of distinctly structured CagA proteins in Western and East Asian H. pylori isolates may underlie the strikingly different incidences of gastric carcinoma in these two geographic areas...
  75. pmc Correlation between PTPN11 gene mutations and congenital heart defects in Noonan and LEOPARD syndromes
    A Sarkozy
    J Med Genet 40:704-8. 2003
  76. ncbi Selective down-regulation of angiotensin II receptor type 1A signaling by protein tyrosine phosphatase SHP-2 in vascular smooth muscle cells
    Thanh Doan
    Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
    Cell Signal 16:301-11. 2004
    ..These data show SHP-2 represents a critical negative regulator of angiotensin II signaling, and further demonstrate a new function for this phosphatase in vascular smooth muscle cells...
  77. ncbi Helicobacter pylori CagA induces Ras-independent morphogenetic response through SHP-2 recruitment and activation
    Hideaki Higashi
    Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University, Kita 15, Nishi 7, Kita ku, Sapporo 060 0815, Japan
    J Biol Chem 279:17205-16. 2004
    ..Our work therefore suggests a key role of SHP-2 in the pathological activity of H. pylori virulence factor CagA...
  78. ncbi Genotype-phenotype correlations in Noonan syndrome
    Martin Zenker
    Institute of Human Genetics, Departments of Pediatric Endocrinology and Pediatric Cardiology, University Children s Hospital, Erlangen, Germany
    J Pediatr 144:368-74. 2004
    ..Mutational analysis was performed by direct sequencing of the entire coding sequence of the PTPN11 gene...
  79. pmc Interaction of the tyrosine phosphatase SHP-2 with Gab2 regulates Rho-dependent activation of the c-fos serum response element by interleukin-2
    Mary Arnaud
    INSERM U461, Faculte de Pharmacie Paris XI, 5 Rue Jean Baptiste Clement, 92290 Chatenay Malabry, France
    Biochem J 382:545-56. 2004
    ..Our studies thus provide new insights into the role of Gab2 and SHP-2 in IL-2 signal transduction...
  80. pmc Human somatic PTPN11 mutations induce hematopoietic-cell hypersensitivity to granulocyte-macrophage colony-stimulating factor
    Rebecca J Chan
    Herman B Wells Center for Pediatric Research, 1044 W Walnut St, R4 402, Indianapolis, IN 46202, USA
    Blood 105:3737-42. 2005
    Juvenile myelomonocytic leukemia (JMML) is a lethal disease of young children characterized by hypersensitivity of hematopoietic progenitors to granulocyte-macrophage colony-stimulating factor (GM-CSF)...
  81. ncbi Association between serum pepsinogens and polymorphismof PTPN11 encoding SHP-2 among Helicobacter pylori seropositive Japanese
    Yasuyuki Goto
    Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan
    Int J Cancer 118:203-8. 2006
    ..The functional consequences of the G/A polymorphism remain to be elucidated...
  82. ncbi Structural and functional effects of disease-causing amino acid substitutions affecting residues Ala72 and Glu76 of the protein tyrosine phosphatase SHP-2
    Gianfranco Bocchinfuso
    Dipartimento di Scienze e Tecnologie Chimiche, Universita di Roma Tor Vergata, Rome, Italy
    Proteins 66:963-74. 2007
    ....
  83. ncbi Shp2-mediated molecular signaling in control of embryonic stem cell self-renewal and differentiation
    Gen Sheng Feng
    Programs in Signal Transduction and Stem Cells and Regeneration, Burnham Institute for Medical Research, 10901 N Torrey Pines Rd, La Jolla, CA 92037, USA
    Cell Res 17:37-41. 2007
    ..This short review discusses the physiological role of Shp2, a cytoplasmic tyrosine phosphatase, in the molecular switch governing ES cell self-renewal versus differentiation...
  84. pmc Grb2-associated binder 1 polymorphism was associated with the risk of Helicobactor pylori infection and gastric atrophy
    Yasuyuki Goto
    Department of Preventive Medicine Biostatistics and Medical Decision Making, Nagoya University Graduate School of Medicine, Nagoya 466 8550, Japan
    Int J Med Sci 4:1-6. 2006
    ..binder 1 (Gab1) polymorphism and the combination of PTPN11 gene encoding src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP2) and Gab1 gene with gastric cancer and gastric atrophy among H. pylori seropositive subjects.
  85. pmc Interaction of scaffolding adaptor protein Gab1 with tyrosine phosphatase SHP2 negatively regulates IGF-I-dependent myogenic differentiation via the ERK1/2 signaling pathway
    Tatsuya Koyama
    Department of Structural Analysis, National Cardiovascular Center Research Institute, 5 7 1 Fujishirodai, Suita, Osaka, Japan
    J Biol Chem 283:24234-44. 2008
    ..Gab1 underwent tyrosine phosphorylation and subsequent complex formation with protein-tyrosine phosphatase SHP2 upon IGF-I stimulation in C2C12 myoblasts...
  86. pmc Molecular mechanism for SHP2 in promoting HER2-induced signaling and transformation
    Xiangdong Zhou
    Department of Biochemistry and The Marry Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia 26506, USA
    J Biol Chem 284:12226-34. 2009
    The Src homology phosphotyrosyl phosphatase 2 (SHP2) plays a positive role in HER2-induced signaling and transformation, but its mechanism of action is poorly understood...
  87. pmc SHP-2 expression negatively regulates NK cell function
    Amanda K Purdy
    Fox Chase Cancer Center, Institute for Cancer Research, Philadelphia, PA 19111, USA
    J Immunol 183:7234-43. 2009
    ..This suppression of activation impacts microtubule organizing center-based cytoskeletal rearrangement and granule release...
  88. pmc Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo
    M Kamran Ikram
    Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
    PLoS Genet 6:e1001184. 2010
    ..These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease...
  89. pmc Tyrosine phosphatase SHP2 regulates the expression of acyl-CoA synthetase ACSL4
    Mariana Cooke
    Department of Biochemistry, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina
    J Lipid Res 52:1936-48. 2011
    ..NSC87877, a specific inhibitor of the tyrosine phosphatase SHP2, reduced ACSL4 protein levels in ACSL4-rich breast cancer cells and steroidogenic cells...
  90. doi SHP-2 and PTP-pest induction during Rb-E2F associated apoptosis
    Liza D Morales
    Department of Biology, The University of Texas Pan American, Edinburg, TX, USA
    Cell Mol Biol Lett 17:422-32. 2012
    ..This report identifies two additional PTPs, SHP-2 and PTP-PEST, that are also directly activated by the Rb-E2F pathway and which can contribute to signal transduction during p53-independent apoptosis...
  91. pmc Role of SHP2 phosphatase in KIT-induced transformation: identification of SHP2 as a druggable target in diseases involving oncogenic KIT
    Raghuveer Singh Mali
    Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Blood 120:2669-78. 2012
    ..We show that SHP2 phosphatase is essential for oncogenic KIT-induced growth and survival in vitro and myeloproliferative disease (MPD)..
  92. doi Dual faces of SH2-containing protein-tyrosine phosphatase Shp2/PTPN11 in tumorigenesis
    Shuangwei Li
    Department of Pathology, and Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093 0864, USA
    Front Med 6:275-9. 2012
    PTPN11, which encodes tyrosine phosphatase Shp2, is a critical gene mediating cellular responses to hormones and cytokines...
  93. ncbi Selective sequestration of STAT1 in the cytoplasm via phosphorylated SHP-2 ameliorates murine experimental colitis
    Xingxin Wu
    State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China
    J Immunol 189:3497-507. 2012
    ..These findings could lead to increased options for the treatment of Crohn's disease and other Th1-mediated inflammatory diseases...
  94. pmc Epithelial tyrosine phosphatase SHP-2 protects against intestinal inflammation in mice
    Genevieve Coulombe
    Département d Anatomie et de Biologie Cellulaire, Universite de Sherbrooke, Sherbrooke, Quebec, Canada
    Mol Cell Biol 33:2275-84. 2013
    ..Finally, SHP-2 mRNA levels were significantly reduced in intestinal biopsy specimens from UC patients. Our results establish intestinal epithelial SHP-2 as a critical determinant for prevention of gut inflammation...
  95. ncbi Interleukin (IL)-3 and granulocyte/macrophage colony-stimulating factor, but not IL-4, induce tyrosine phosphorylation, activation, and association of SHPTP2 with Grb2 and phosphatidylinositol 3'-kinase
    M J Welham
    Biomedical Research Centre, University of British Columbia, Vancouver, Canada
    J Biol Chem 269:23764-8. 1994
    ..These results suggest that SHPTP2 may play an important role in integrating signals from the IL-3 and GM-CSF receptors to both Ras and PI 3'-kinase...
  96. ncbi Involvement of SH2-containing phosphotyrosine phosphatase Syp in erythropoietin receptor signal transduction pathways
    T Tauchi
    Department of Medicine Hematology Oncology, Indiana University School of Medicine, Indianapolis 46202
    J Biol Chem 270:5631-5. 1995
    ..These results suggest that Syp may be an important signaling component downstream of the EpoR and may regulate the proliferation and differentiation of hematopoietic cells...
  97. ncbi Activation of a phosphotyrosine phosphatase by tyrosine phosphorylation
    W Vogel
    Department of Molecular Biology, Max Planck Institut fur Biochemie, Martinsried, Germany
    Science 259:1611-4. 1993
    ..The phosphotyrosine phosphatase 1D (PTP 1D) contains two amino terminally located Src homology 2 (SH2) domains and is similar to the Drosophila corkscrew ..
  98. ncbi Activation of the SH2-containing phosphotyrosine phosphatase SH-PTP2 by its binding site, phosphotyrosine 1009, on the human platelet-derived growth factor receptor
    R J Lechleider
    Molecular Medicine Unit, Beth Israel Hospital, Boston, Massachusetts
    J Biol Chem 268:21478-81. 1993
    ..we and others molecularly cloned a ubiquitously expressed SH2 domain-containing PTP, SH-PTP2 (Syp, PTP1D, PTP2C), and found that it interacts directly with several activated growth factor receptors via its SH2 domains...
  99. pmc Role of SH-PTP2, a protein-tyrosine phosphatase with Src homology 2 domains, in insulin-stimulated Ras activation
    T Noguchi
    Second Department of Internal Medicine, Kobe University School of Medicine, Japan
    Mol Cell Biol 14:6674-82. 1994
    ....
  100. pmc Protein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor receptor beta to Ras
    A M Bennett
    Molecular Medicine Unit, Beth Israel Hospital, Boston, MA 02215
    Proc Natl Acad Sci U S A 91:7335-9. 1994
    Protein-tyrosine-phosphatase SHPTP2 (Syp/PTP-1D/PTP2C) is the homologue of the Drosophila corkscrew (csw) gene product, which transmits positive signals from receptor tyrosine kinases...
  101. ncbi A tyrosine-phosphorylated 110-120-kDa protein associates with the C-terminal SH2 domain of phosphotyrosine phosphatase-1D in T cell receptor-stimulated T cells
    J A Frearson
    Department of Immunology, The Babraham Institute, Cambridge, GB
    Eur J Immunol 26:1539-43. 1996
    ..This currently unidentified phosphotyrosine protein may be involved in localizing PTP-1D to the TCR following receptor stimulation...

Research Grants68

  1. Cardiofaciocutaneous Syndrome & Noonan Syndrome Meeting
    Amy Roberts; Fiscal Year: 2006
    ..the public and medical professionals, and facilitate research on two rare genetic disorders, Cardiofaciocutaneous (CFC) syndrome and Noonan syndrome...
  2. Shyam S Mohapatra; Fiscal Year: 2015
    ..of this proposal is to investigate the mechanism whereby respiratory syncytial virus (RSV) nonstructural protein 1 (NS1) modulates innate immunity and cell survival through the mitochondrial system following RSV infection, and to ..
  3. Zhong Yin Zhang; Fiscal Year: 2016
    ..This competitive renewal focuses on SHP2 (Src homology 2 (SH2)-domain containing protein tyrosine phosphatase-2), which is the first bona fide oncoprotein ..
  4. MARIA IRENE KONTARIDIS; Fiscal Year: 2016
    ..Mutations in PTPN11, the gene encoding the protein tyrosine phosphatase (PTP) Shp2, are directly implicated in CHD, causing ~50% of Noonan Syndrome (NS) and nearly all LEOPARD Syndrome (LS) cases...
  5. Molecular Pathogenesis of the Cardiomyogenic Defects in LEOPARD Syndrome
    MARIA IRENE KONTARIDIS; Fiscal Year: 2010
    SUMMARY: Recently, mutations in the SH2 domain-containing protein tyrosine phosphatase Shp2, have been implicated in cardiac disease...
  6. STRUCTURES OF RNA BINDING PROTEINS FROM INFLUENZA VIRUS
    Gaetano Montelione; Fiscal Year: 2000
    ..be developed primarily o domains os a biomedically-important RNA- binding protein, the nonstructural protein 1 (NS1 protein) from influenza virus and complexes between the RNA-binding domain of the NS1 protein and its specific RNA ..
  7. Zhong Yin Zhang; Fiscal Year: 2014
    ..The long-term objective of the proposed research program is to develop small molecule therapeutics targeting SHP2 (Src homology 2 domain-containing phosphatase 2), which is the first bona fide oncogene identified in the PTP ..
  8. Role of PTPN11 Mutations in Myeloid Leukemogenesis
    Kevin M Shannon; Fiscal Year: 2010
    ..we identified somatic mutations in the PTPN11 gene in ~35% of patients with juvenile myelomonocytic leukemia (JMML) and in ~5% of acute myeloid leukemias...
  9. MMDx: A rapid multiplexed matrix code diagnostic for real time epidemiology
    Lee Gehrke; Fiscal Year: 2013
    ..offer 1) direct identification of the four different dengue virus serotypes by detecting circulating viral protein NS1, as well as 2) indirect Ebola virus and dengue virus identification by detecting circulating antibodies against the ..
  10. Dengue diagnostics using a novel peroxidase chain reaction (PxCR)
    PETER PETER ZASSENHAUS; Fiscal Year: 2013
    ..3) Develop a PxCR assay for the detection of pan-dengue NS1 protein...
  11. SIGNAL TRANSDUCTION BY NON-TRANSMEMBRANE PTPS
    Benjamin G Neel; Fiscal Year: 2013
    ..goal of our research is to understand the biological function, mechanism of action, and role in disease ofthe PTPs Shp2 and PTPIB...
  12. Anton M Bennett; Fiscal Year: 2015
    ..The identification of targets involved in CHD will also reveal new modes of therapeutic strategies in which to treat, and prognostic tools in which to evaluate, NS-related CHD. ..
  13. Forest M White; Fiscal Year: 2014
    ..Aim 3 comprises further pre-clinical validation studies of MEK-inhibitors and other therapeutic agents for NS-associated HCM. ..
  14. NEUROFIBROMIN, NEURAL CREST AND CARDIAC DEVELOPMENT
    Jonathan A Epstein; Fiscal Year: 2012
    ..Many aspects of Nf1 loss of function are recapitulated in mice and humans by activating mutations in Shp2, a protein phosphatase that modulates diverse intracellular signaling pathways and which is mutated in Noonan ..
  15. Aberrant Monocytic Differentiation Induced by Gain-of-Function Shp2 Mutants
    Rebecca J Chan; Fiscal Year: 2010
    ..In addition to GM-CSF-stimulated hyperproliferation and elevated levels of phospho-Erk, we found that activating Shp2 mutations (Shp2E76K and Shp2D61Y) promote a shift toward monocytic differentiation at the expense of other myeloid ..
  16. Drosophila models of human cognitive disorders: NF1 and Noonan syndrome
    Yi Zhong; Fiscal Year: 2012
    ..Study of these mutations will allow us gaining insights into molecular basis underlying memory retrieval and memory formation. Such understanding will in turn facilitate development of treatment for the disorders. ..
  17. Third International Meeting on Genetic Syndromes of the Ras/MAPK Pathway
    Bruce R Korf; Fiscal Year: 2013
    ..This meeting will be held in conjunction with family forums of the CSFN, CFC International, Noonan Syndrome Support Group, and neurofibromatosis support groups...
  18. Ileana M Cristea; Fiscal Year: 2014
    ..transcription factors TBX5, the zinc finger transcription factor CASZ1, and the non-receptor protein phosphatase SHP2. We have focused on these proteins based on their evolutionary conservation in sequence, expression, and function, ..
  19. Targeting SHP2 Phosphatase for Hematologic Malignancies in Noonan Syndrome
    Cheng Kui Qu; Fiscal Year: 2012
    ..developmental disorder Noonan syndrome and various childhood leukemias, such as juvenile myelomonocytic leukemia (JMML), B-cell acute lymphoblastic leukemia (B-ALL), and acute myeloid leukemia (AML)...
  20. Understanding intellectual disability in Noonan syndrome and related disorders
    Bruce D Gelb; Fiscal Year: 2013
    ..e., CBL, SHP2, SOS, RAS, RAF and MEK proteins)...
  21. International Meeting on Genetic Syndromes of the Ras/MAPK Pathway
    Bruce D Gelb; Fiscal Year: 2011
    ..This meeting will be held in conjunction with family meetings of the CSFN, CFC International, Noonan Syndrome Support Group, and neurofibromatosis support groups...
  22. Requirements for the FGF/MAPK in early heart development
    Frank Conlon; Fiscal Year: 2007
    ..abstract_text> ..
  23. Gadiparthi N Rao; Fiscal Year: 2016
    ..activates GRB2-associated binding protein 1 (Gab1) and Src homology 2- containing protein tyrosine phosphatase (Shp2), whose stimulation is otherwise expected in response to EGFR activation by its true ligand, EGF, and the ..
  24. AMY CELESTE MORRISON; Fiscal Year: 2014
    ..can trigger contact cluster investigations that effectively capture individuals positive for DENV antigen or RNA by NS1 or qPCR, including inapparent or mild disease cases, for enrollment in feeding protocols...
  25. Reuben Kapur; Fiscal Year: 2015
    ..Expression of the Shp2 protein tyrosine phosphatase is consistently elevated in primary leukemia cell specimens from multiple adult acute ..
  26. Gloria Lee; Fiscal Year: 2016
    ..In addition, we found that tau associated with the protein tyrosine phosphatase SHP2 in an NGF-dependent manner...
  27. Shp2 in Osteoclastogenesis and Bone Remodeling
    Wentian Yang; Fiscal Year: 2010
    ..goal of this proposal is to elucidate the function of protein tyrosine phosphatases (PTP), specifically PTP Shp2, in osteoclastogenesis and bone remodeling...
  28. Role of Gab2 and Shp2 in Hematopoietic Signalling
    Benjamin G Neel; Fiscal Year: 2010
    ..The long range goal of this research is to understand the function of the SH2-containing PTP Shp2 (PTPn11) and its binding protein, Gab2, in normal hematopoiesis and disease...
  29. Jie Wu; Fiscal Year: 2016
    ..The goal of this study is to investigate the roles of PTPN11 (SHP2) in epithelial tumors focusing on lung adenocarcinoma...
  30. MARIA IRENE KONTARIDIS; Fiscal Year: 2014
    ..proposal will determine whether aberrant regulation of the small GTPase RhoA by the protein tyrosine phosphatase Shp2 is directly involved in mediating IDC pathogenesis...
  31. CHARLES B GOODWIN; Fiscal Year: 2014
    ..Ras signaling pathway, including activating mutations in PTPN11, which encodes the protein tyrosine phosphatase, Shp2. It has been shown that, in response to GM-CSF stimulation, gain-of-function mutations in Shp2 result in elevated ..
  32. Chen Yan; Fiscal Year: 2014
    ..1). Recently, SHP2, a protein tyrosine phosphatase (PTPase), was shown to stimulate the Apoptosis Signal-regulated Kinase (ASK1)-JNK-..
  33. Improved Therapies for AML in the Elderly
    SARAH C NABINGER; Fiscal Year: 2011
    ..Tyrosine 599 (Y599) on WT-Flt3 has been shown to recruit the protein tyrosine phosphatase, Shp2, upon Flt3 ligand (FL) stimulation and normally activates the mitogen activated protein kinase, Erk...
  34. Stem Cell Biology: New Directions in Clinical and Basic Research
    Peter J Quesenberry; Fiscal Year: 2011
    ..The current three projects are: 1) Injured lung and its influence on marrow cell phenotype, 2) Tyrosine phosphatase Shp2 in stem cell property maintenance, and 3) Determining the transcriptional regulation and cell signaling events that ..
  35. Maike Krenz; Fiscal Year: 2016
    ..A candidate master regulator of cardiac stress adaptation is the protein tyrosine phosphatase SHP2. SHP2 is indispensable in the developing heart, but whether SHP2 actively supports cardiac homeostasis throughout ..
  36. Modulation of ErbB Signaling
    Jie Wu; Fiscal Year: 2009
    ..The Shp2 protein tyrosine phosphatase is activated by ErbB and other protein tyrosine kinases to regulate cell signaling...
  37. JARED TYLER AHRENDSEN; Fiscal Year: 2015
    ..We will focus on the protein tyrosine phosphatase Shp2, which may act as a brake to active myelination...
  38. Xin Zhang; Fiscal Year: 2016
    ..We have identified Shp2, a protein tyrosine phosphatase, as a key factor in orchestrating lens morphogenesis by regulating FGF signaling...
  39. SHP2 and SIRP modulate erbB signals in astrocytes
    DONALD O ROURKE; Fiscal Year: 2005
    ..The proposed set of studies will examine the roles of the SH2 domain-containing SHP2 protein-tyrosine phosphatase (PTP) and the immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing SIRP (..
  40. SHP2 and SIRP modulate erbB signals in astrocytes
    DONALD O ROURKE; Fiscal Year: 2007
    ..We have focused on mechanisms by which the SHP2 protein tyrosine phosphatase (FTP) and the SIRP inhibitory adhesion receptor modulate EGFR/erbB signals in normal ..
  41. SH2 DOMAIN CONTAINING PTPASES SHP1 AND 2
    Tomas Mustelin; Fiscal Year: 1999
    ..tyrosine phosphatase (PTPase), CD45, has so far been found to be important, while two other PTPases, SHP1 and SHP2, may participate...
  42. Yaya Wang; Fiscal Year: 2014
    ..In this grant I wil study the function of a genetic variant associated with multiple autoimmune diseases, the PTPN22 1858T variant, to examine its role in immune responses and disease pathogenesis. ..
  43. TH1 AND TH2 RESPONSES IN VIRAL IMMUNITY
    Thomas M Moran; Fiscal Year: 2010
    ..Surprisingly influenza virus is a very poor stimulator of DC maturation in vitro because the viral NS1 protein inhibits the maturation process...
  44. Genetic Syndromes of the Ras/MAPK Pathway: From Bedside to Bench and Back
    KATHERINE RAUEN; Fiscal Year: 2009
    ..This meeting will be held in conjunction with the biannual family meetings of the CSFN, CFC International, Noonan Syndrome Support Group, and the neurofibromatosis support groups...
  45. HoxA10 Function During Myeloid Differentiation
    ELIZABETH ANN EKLUND; Fiscal Year: 2011
    ..myeloid cells, we found that HoxA10 is maintained in a non-tyrosine phosphorylated state by SHP1 and SHP2 protein tyrosine phosphatases...
  46. Rapid Heart Attack Detection using an AC Electrokinetic Device
    Rajaram Krishnan; Fiscal Year: 2011
    ..It has also been reported that the elevated levels of CFC-DNA is a strong prognostic marker in acute MI...
  47. Jacob V P Eswarakumar; Fiscal Year: 2014
    ..of six tyrosine residues on Frs21, which in turn serve as docking sites for the recruitment of four Grb2 and two Shp2 signaling molecules...
  48. Influenza therapy by Au-nanorod 5'PPP-NS1-siRNA/cDNA targeting of bronchial cells
    Paul R Knight; Fiscal Year: 2010
    ..just recently been synthesized, have dual actions of suppressing the translation of the influenza virulence factor, NS1, as well as independently stimulating type I interferon production through activation of the RIG-I pathway...
  49. Novel mouse models of inflammation-resolution
    Paul L Fox; Fiscal Year: 2010
    ..Glu-Pro-tRNA synthetase (EPRS), ribosomal protein L13a, glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and NS1-associated protein (NSAP1 or hnRNP Q)...
  50. Jie Wu; Fiscal Year: 2014
    ..derived from different lines of existing Cre-RMCE-capable transgenic mice to replace the original floxed tetO- SHP2 transgenes with tetO-KIF5B-RET...
  51. Host-pathogen competition in IFN mediated antiviral defense
    Jae U Jung; Fiscal Year: 2013
    ..interacts with host cells to evade intracellular innate immunity;and Project 5 studies how the influenza A virus NS1 protein prevents cytoplasmic viral sensors from recognizing viral infections, us, the goal of this U19 project is ..
  52. Michael G Roth; Fiscal Year: 2014
    ..As an example, the NS1 protein of influenza virus, a major virulence factor, inhibits host gene expression and signal transduction ..
  53. Genetic Determinants of Physiological Responses to Fluoride in Bone
    Eric T Everett; Fiscal Year: 2012
    ..of bone formation/resorption;ex vivo osteoclastogenesis and osteoprogenitor assays;and ex vivo hematopoietic (CFC) assays will be performed. Additionally, selected bones will be phenotyped for BMD (microCT)...
  54. PERINATAL METABOLIC AND HORMONAL EFFECTS
    Sherin U Devaskar; Fiscal Year: 2010
    ..a) leptin and insulin receptor cross-talk signaling pathways by assessing the ObRb-JAK2-STAT3/SOCS3-SHP2-PTP1B and the IRbeta tyrosine kinase-IRS1/2-P-l-3-kinase- PDK1/2-Akt1/2/PKC;-PDE38-cAMP pathways and b) the ..
  55. Robert M Krug; Fiscal Year: 2016
    ..Several of these interactions reveal new targets for antiviral development. The NS1 protein of influenza A viruses (NS1A) has important roles in virus infection and virulence...
  56. Inflammatory Response in Influenza Virus Infection
    Thomas M Moran; Fiscal Year: 2010
    ..We have observed a delayed inflammatory response that we ascribe to the impact of the immune antagonist protein, NS1. Once inflammation has been activated high levels of cytokine/chemokines/growth factors can be demonstrated in the ..
  57. Carole Ober; Fiscal Year: 2016
    ..genetic variation in the LILRB receptors modulate the effects of HLA-G on both T cell phenotype and on the SHP1 and SHP2 signaling pathways that modulate airway smooth muscle hypertrophy in chronic asthma...
  58. Anthony N van den Pol; Fiscal Year: 2015
    ..reporter, and virally infected cells are detected by green immunofluorescent staining for the LuIII viral antigen NS1. A critical clinical problem with glioma is their recurrence after surgical or radiation treatment;here we tes the ..
  59. Jacob V P Eswarakumar; Fiscal Year: 2014
    ..In Aim 2, we will determine the role of Frs21-mediated Grb2 and Shp2 signaling pathways in SMG branching morphogenesis...
  60. Protein-thiol mixed disulfide in cataractogenesis
    Marjorie F Lou; Fiscal Year: 2013
    ..assays of denucleation enzymes (DNase II[unreadable] and ubiquitin) and bFGF-specific phosphatases (PTEN and Shp2)...
  61. Live attenuated vaccines for epidemic and pandemic flu
    Adolfo Garcia Sastre; Fiscal Year: 2010
    ..investigate a novel concept for the design of improved influenza virus vaccines based on modification of the viral NS1 gene to generate live attenuated vaccine strains...
  62. Z Hong Zhou; Fiscal Year: 2015
    ..In addition, our preliminary data shows that non-structural protein NS1 has a role on virus release and forms highly ordered helical tubules in a Zn2+-dependent manner, thus providing an ..
  63. KENDRA BENCE; Fiscal Year: 2015
    ..PTPs) have recently been implicated in regulation of the leptin signaling pathway in the brain: PTP1B and SHP2. These PTPs clearly have important in vivo roles in regulating energy balance, but the precise neuronal site(s) of ..
  64. Nox4 and Cardiac Fibrosis
    Dan Sorescu; Fiscal Year: 2012
    ..that Nox4-released ROS are essential for Ang II and TGF-1-induced fibrosis by inhibiting the tyrosine-phosphatase Shp2 that negatively regulates the activation and nuclear cooperation of transcription factors Smad2/3 and FoxO3A...