Ptpn11

Summary

Gene Symbol: Ptpn11
Description: protein tyrosine phosphatase, non-receptor type 11
Alias: 2700084A17Rik, AW536184, PTP1D, PTP2C, SAP-2, SH-PTP2, SH-PTP3, SHP-2, Shp2, Syp, tyrosine-protein phosphatase non-receptor type 11, SH2 domain-containing protein tyrosine phosphatase-2, protein-tyrosine phosphatase SYP
Species: mouse
Products:     Ptpn11

Top Publications

  1. Princen F, Bard E, Sheikh F, Zhang S, Wang J, Zago W, et al. Deletion of Shp2 tyrosine phosphatase in muscle leads to dilated cardiomyopathy, insulin resistance, and premature death. Mol Cell Biol. 2009;29:378-88 pubmed publisher
    ..We report here that selective deletion of Shp2, an SH2-containing cytoplasmic tyrosine phosphatase, in striated muscle results in severe dilated cardiomyopathy in ..
  2. Chan R, Li Y, Hass M, Walter A, Voorhorst C, Shelley W, et al. Shp-2 heterozygous hematopoietic stem cells have deficient repopulating ability due to diminished self-renewal. Exp Hematol. 2006;34:1230-9 pubmed
  3. Chen Y, Wen R, Yang S, Schuman J, Zhang E, Yi T, et al. Identification of Shp-2 as a Stat5A phosphatase. J Biol Chem. 2003;278:16520-7 pubmed
    ..Therefore, we conclude that Shp-2 is a Stat5A phosphatase, which down-regulates the active Stat5A in vivo. ..
  4. Owen C, Czopek A, Agouni A, Grant L, Judson R, Lees E, et al. Adipocyte-specific protein tyrosine phosphatase 1B deletion increases lipogenesis, adipocyte cell size and is a minor regulator of glucose homeostasis. PLoS ONE. 2012;7:e32700 pubmed publisher
    ..Moreover, PTP1B does not appear to be the major negative regulator of the IR in adipocytes. ..
  5. Ke Y, Zhang E, Hagihara K, Wu D, Pang Y, Klein R, et al. Deletion of Shp2 in the brain leads to defective proliferation and differentiation in neural stem cells and early postnatal lethality. Mol Cell Biol. 2007;27:6706-17 pubmed
    ..We show here that Shp2, an introcellular tyrosine phosphatase with two SH2 domains, plays a critical role in NSC activities...
  6. Feng G, Shen R, Heng H, Tsui L, Kazlauskas A, Pawson T. Receptor-binding, tyrosine phosphorylation and chromosome localization of the mouse SH2-containing phosphotyrosine phosphatase Syp. Oncogene. 1994;9:1545-50 pubmed
    The murine phosphotyrosine phosphatase, Syp, is a widely-expressed cytoplasmic enzyme that contains two SH2 domains...
  7. Uhlen P, Burch P, Zito C, Estrada M, Ehrlich B, Bennett A. Gain-of-function/Noonan syndrome SHP-2/Ptpn11 mutants enhance calcium oscillations and impair NFAT signaling. Proc Natl Acad Sci U S A. 2006;103:2160-5 pubmed
    Gain-of-function mutations in SHP-2/PTPN11 cause Noonan syndrome, a human developmental disorder...
  8. Qin X, Zhang G, Zhang X, Qiu Z, Wang P, Li Y, et al. Protein tyrosine phosphatase SHP2 regulates TGF-?1 production in airway epithelia and asthmatic airway remodeling in mice. Allergy. 2012;67:1547-56 pubmed publisher
    ..The protein tyrosine phosphatase SHP2 is a demonstrable modulator of TGF-?1 production and thus a potential regulator of airway remodeling...
  9. Muller J, Schönherr C, Markova B, Bauer R, Stocking C, Bohmer F. Role of SHP2 for FLT3-dependent proliferation and transformation in 32D cells. Leukemia. 2008;22:1945-8 pubmed publisher

More Information

Publications80

  1. Zhang L, Friedman A. SHP2 tyrosine phosphatase stimulates CEBPA gene expression to mediate cytokine-dependent granulopoiesis. Blood. 2011;118:2266-74 pubmed publisher
    G-CSF signals contribute to granulocyte lineage specification. We previously found that G-CSF induces SHP2 tyrosine phosphorylation and that chemical inhibition of SHP1/SHP2 reduces CFU-G and prevents G-CSF but not M-CSF activation of ERK...
  2. Zhu H, Ji K, Alderson N, He Z, Li S, Liu W, et al. Kit-Shp2-Kit signaling acts to maintain a functional hematopoietic stem and progenitor cell pool. Blood. 2011;117:5350-61 pubmed publisher
    ..Inducible ablation of PTPN11/Shp2 resulted in severe cytopenia in BM, spleen, and peripheral blood in mice...
  3. Araki T, Chan G, Newbigging S, Morikawa L, Bronson R, Neel B. Noonan syndrome cardiac defects are caused by PTPN11 acting in endocardium to enhance endocardial-mesenchymal transformation. Proc Natl Acad Sci U S A. 2009;106:4736-41 pubmed publisher
    ..Germline-activating mutations in PTPN11, which encodes the protein tyrosine phosphatase SHP2, cause about half of NS cases; other causative alleles ..
  4. Saxton T, Ciruna B, Holmyard D, Kulkarni S, Harpal K, Rossant J, et al. The SH2 tyrosine phosphatase shp2 is required for mammalian limb development. Nat Genet. 2000;24:420-3 pubmed
    ..Comparison of Ptpn11 (encoding Shp2)-mutant and Fgfr1 (encoding fibroblast growth factor receptor-1)-mutant chimaeric limbs indicated ..
  5. Feng G, Hui C, Pawson T. SH2-containing phosphotyrosine phosphatase as a target of protein-tyrosine kinases. Science. 1993;259:1607-11 pubmed
    A mouse phosphotyrosine phosphatase containing two Src homology 2 (SH2) domains, Syp, was identified...
  6. Lapinski P, Meyer M, Feng G, Kamiya N, King P. Deletion of SHP-2 in mesenchymal stem cells causes growth retardation, limb and chest deformity, and calvarial defects in mice. Dis Model Mech. 2013;6:1448-58 pubmed publisher
    In mice, induced global disruption of the Ptpn11 gene, which encodes the SHP-2 tyrosine phosphatase, results in severe skeletal abnormalities...
  7. Müller M, Klaile E, Vorontsova O, Singer B, Obrink B. Homophilic adhesion and CEACAM1-S regulate dimerization of CEACAM1-L and recruitment of SHP-2 and c-Src. J Cell Biol. 2009;187:569-81 pubmed publisher
    ..These data suggest that transmembrane signaling by CEACAM1 operates by alteration of the monomer/dimer equilibrium, which leads to changes in the SHP-2/c-Src-binding ratio. ..
  8. Yuan L, Yu W, Qu C. DNA damage-induced G2/M checkpoint in SV40 large T antigen-immortalized embryonic fibroblast cells requires SHP-2 tyrosine phosphatase. J Biol Chem. 2003;278:42812-20 pubmed
    ..These results together provide the first evidence that SHP-2 tyrosine phosphatase enhances the DNA damage G2/M checkpoint in SV40 large T antigen immortalized murine embryonic fibroblast cells. ..
  9. Madhavan R, Zhao X, Ruegg M, Peng H. Tyrosine phosphatase regulation of MuSK-dependent acetylcholine receptor clustering. Mol Cell Neurosci. 2005;28:403-16 pubmed
    ..Immunoscreening identified Shp2 as a major tyrosine phosphatase in C2 myotubes and down-regulation of its expression by RNA interference alleviated ..
  10. Yang W, Klaman L, Chen B, Araki T, Harada H, Thomas S, et al. An Shp2/SFK/Ras/Erk signaling pathway controls trophoblast stem cell survival. Dev Cell. 2006;10:317-27 pubmed
    ..We analyzed mice with a null mutation of Shp2 (Ptpn11), a key component of receptor tyrosine kinase signaling...
  11. Yu W, Daino H, Chen J, Bunting K, Qu C. Effects of a leukemia-associated gain-of-function mutation of SHP-2 phosphatase on interleukin-3 signaling. J Biol Chem. 2006;281:5426-34 pubmed
  12. Qu C, Yu W, Azzarelli B, Cooper S, Broxmeyer H, Feng G. Biased suppression of hematopoiesis and multiple developmental defects in chimeric mice containing Shp-2 mutant cells. Mol Cell Biol. 1998;18:6075-82 pubmed
    ..More importantly, the requirement for Shp-2 is more stringent in hematopoiesis than in other systems. ..
  13. Coulombe G, Leblanc C, Cagnol S, Maloum F, Lemieux E, Perreault N, et al. Epithelial tyrosine phosphatase SHP-2 protects against intestinal inflammation in mice. Mol Cell Biol. 2013;33:2275-84 pubmed publisher
    Polymorphisms of PTPN11 encoding SHP-2 are biomarkers for ulcerative colitis (UC) susceptibility. However, their functional relevance is unknown. We thus investigated the role of epithelial SHP-2 in the control of intestinal homeostasis...
  14. Arrandale J, Gore Willse A, Rocks S, Ren J, Zhu J, Davis A, et al. Insulin signaling in mice expressing reduced levels of Syp. J Biol Chem. 1996;271:21353-8 pubmed
    b>Syp is a protein tyrosine phosphatase implicated in insulin and growth factor signaling. To evaluate the role of syp in insulin's regulation of plasma glucose, we generated knockout mice. Homozygous knockout mice die prior to day 10...
  15. Saxton T, Henkemeyer M, Gasca S, Shen R, Rossi D, Shalaby F, et al. Abnormal mesoderm patterning in mouse embryos mutant for the SH2 tyrosine phosphatase Shp-2. EMBO J. 1997;16:2352-64 pubmed
    ..Thus, Shp-2 modulates tyrosine kinase signalling in vivo and is crucial for gastrulation during mammalian development. ..
  16. Zhang S, Yang W, Kontaridis M, Bivona T, Wen G, Araki T, et al. Shp2 regulates SRC family kinase activity and Ras/Erk activation by controlling Csk recruitment. Mol Cell. 2004;13:341-55 pubmed
    The protein-tyrosine phosphatase Shp2 plays an essential role in growth factor and integrin signaling, and Shp2 mutations cause developmental defects and/or malignancy. Previous work has placed Shp2 upstream of Ras...
  17. Schubbert S, Lieuw K, Rowe S, Lee C, Li X, Loh M, et al. Functional analysis of leukemia-associated PTPN11 mutations in primary hematopoietic cells. Blood. 2005;106:311-7 pubmed
    b>PTPN11 encodes the protein tyrosine phosphatase SHP-2, which relays signals from growth factor receptors to Ras and other effectors...
  18. Ke Y, Lesperance J, Zhang E, Bard Chapeau E, Oshima R, Muller W, et al. Conditional deletion of Shp2 in the mammary gland leads to impaired lobulo-alveolar outgrowth and attenuated Stat5 activation. J Biol Chem. 2006;281:34374-80 pubmed
    ..Phosphotyrosine phosphatase Shp2 has been shown to dephosphorylate and thus inactivate both Stat5 and Stat3 in vitro...
  19. Qu C, Nguyen S, Chen J, Feng G. Requirement of Shp-2 tyrosine phosphatase in lymphoid and hematopoietic cell development. Blood. 2001;97:911-4 pubmed
  20. Agazie Y, Hayman M. Development of an efficient "substrate-trapping" mutant of Src homology phosphotyrosine phosphatase 2 and identification of the epidermal growth factor receptor, Gab1, and three other proteins as target substrates. J Biol Chem. 2003;278:13952-8 pubmed
    Src homology containing phosphotyrosine phosphatase 2 (SHP2) is a positive effector of growth factor, cytokine, and integrin signaling...
  21. Xu D, Wang S, Yu W, Chan G, Araki T, Bunting K, et al. A germline gain-of-function mutation in Ptpn11 (Shp-2) phosphatase induces myeloproliferative disease by aberrant activation of hematopoietic stem cells. Blood. 2010;116:3611-21 pubmed publisher
    Germline and somatic gain-of-function mutations in tyrosine phosphatase PTPN11 (SHP-2) are associated with juvenile myelomonocytic leukemia (JMML), a myeloproliferative disease (MPD) of early childhood...
  22. Zhang E, Chapeau E, Hagihara K, Feng G. Neuronal Shp2 tyrosine phosphatase controls energy balance and metabolism. Proc Natl Acad Sci U S A. 2004;101:16064-9 pubmed
    b>Shp2, a Src homology 2-containing tyrosine phosphatase, has been implicated in a variety of growth factor or cytokine signaling pathways...
  23. Kontaridis M, Eminaga S, Fornaro M, Zito C, Sordella R, Settleman J, et al. SHP-2 positively regulates myogenesis by coupling to the Rho GTPase signaling pathway. Mol Cell Biol. 2004;24:5340-52 pubmed
    ..Collectively, these data provide a mechanistic basis for RhoA activation in myoblasts and demonstrate that myogenesis is critically regulated by the actions of SHP-2 on the p190-B Rho GAP/RhoA pathway. ..
  24. Bard Chapeau E, Li S, Ding J, Zhang S, Zhu H, Princen F, et al. Ptpn11/Shp2 acts as a tumor suppressor in hepatocellular carcinogenesis. Cancer Cell. 2011;19:629-39 pubmed publisher
    The human gene Ptpn11, which encodes the tyrosine phosphatase Shp2, may act as a proto-oncogene because dominantly activating mutations have been detected in several types of leukemia. Herein we report a tumor-suppressor function of Shp2...
  25. He Z, Zhang S, Meng Q, Li S, Zhu H, Raquil M, et al. Shp2 controls female body weight and energy balance by integrating leptin and estrogen signals. Mol Cell Biol. 2012;32:1867-78 pubmed publisher
    ..We show here that Shp2, a nonreceptor tyrosine phosphatase, acts to integrate leptin and estrogen signals...
  26. Nabinger S, Li X, Ramdas B, He Y, Zhang X, Zeng L, et al. The protein tyrosine phosphatase, Shp2, positively contributes to FLT3-ITD-induced hematopoietic progenitor hyperproliferation and malignant disease in vivo. Leukemia. 2013;27:398-408 pubmed publisher
    ..We hypothesized that increased recruitment of the protein tyrosine phosphatase, Shp2, to FLT3-ITDs contributes to FLT3 ligand (FL)-independent hyperproliferation and STAT5 activation...
  27. Vogel W, Lammers R, Huang J, Ullrich A. Activation of a phosphotyrosine phosphatase by tyrosine phosphorylation. Science. 1993;259:1611-4 pubmed
    ..Thus, protein tyrosine kinases and phosphatases do not simply oppose each other's action; rather, they may work in concert to maintain a fine balance of effector activation needed for the regulation of cell growth and differentiation. ..
  28. Kontaridis M, Yang W, Bence K, Cullen D, Wang B, Bodyak N, et al. Deletion of Ptpn11 (Shp2) in cardiomyocytes causes dilated cardiomyopathy via effects on the extracellular signal-regulated kinase/mitogen-activated protein kinase and RhoA signaling pathways. Circulation. 2008;117:1423-35 pubmed publisher
    ..Here, we show that mice with muscle-specific deletion of Ptpn11, the gene encoding the SH2 domain-containing PTP Shp2, rapidly develop a compensated dilated cardiomyopathy ..
  29. Nguyen T, Ke Y, Zhang E, Feng G. Conditional deletion of Shp2 tyrosine phosphatase in thymocytes suppresses both pre-TCR and TCR signals. J Immunol. 2006;177:5990-6 pubmed
    ..We show in this study that Shp2, a close relative of Shp1, plays a positive role in T cell development and functions...
  30. Zhou X, Agazie Y. Molecular mechanism for SHP2 in promoting HER2-induced signaling and transformation. J Biol Chem. 2009;284:12226-34 pubmed publisher
    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...
  31. Bauler T, Kamiya N, Lapinski P, Langewisch E, Mishina Y, Wilkinson J, et al. Development of severe skeletal defects in induced SHP-2-deficient adult mice: a model of skeletal malformation in humans with SHP-2 mutations. Dis Model Mech. 2011;4:228-39 pubmed publisher
    SHP-2 (encoded by PTPN11) is a ubiquitously expressed protein tyrosine phosphatase required for signal transduction by multiple different cell surface receptors...
  32. Marin T, Keith K, Davies B, Conner D, Guha P, Kalaitzidis D, et al. Rapamycin reverses hypertrophic cardiomyopathy in a mouse model of LEOPARD syndrome-associated PTPN11 mutation. J Clin Invest. 2011;121:1026-43 pubmed publisher
    ..caused by catalytically inactivating mutations in the protein tyrosine phosphatase (PTP), non-receptor type 11 (PTPN11) gene that encodes the SH2 domain-containing PTP-2 (SHP2)...
  33. Chan G, Cheung L, Yang W, Milyavsky M, Sanders A, Gu S, et al. Essential role for Ptpn11 in survival of hematopoietic stem and progenitor cells. Blood. 2011;117:4253-61 pubmed publisher
    Src homology 2 domain-containing phosphatase 2 (Shp2), encoded by Ptpn11, is a member of the nonreceptor protein-tyrosine phosphatase family, and functions in cell survival, proliferation, migration, and differentiation in many tissues...
  34. Fornaro M, Burch P, Yang W, Zhang L, Hamilton C, Kim J, et al. SHP-2 activates signaling of the nuclear factor of activated T cells to promote skeletal muscle growth. J Cell Biol. 2006;175:87-97 pubmed
    ..Thus, SHP-2 transduces extracellular matrix stimuli to intracellular signaling pathways to promote skeletal muscle growth. ..
  35. Yu M, Luo J, Yang W, Wang Y, Mizuki M, Kanakura Y, et al. The scaffolding adapter Gab2, via Shp-2, regulates kit-evoked mast cell proliferation by activating the Rac/JNK pathway. J Biol Chem. 2006;281:28615-26 pubmed
    ..Our data show that Gab2 via Shp-2 is critical for transmitting signals from Kit Tyr(567) to activate the Rac/JNK pathway controlling mast cell proliferation, which likely contributes to mast cell development in specific tissues. ..
  36. Chan R, Johnson S, Li Y, Yoder M, Feng G. A definitive role of Shp-2 tyrosine phosphatase in mediating embryonic stem cell differentiation and hematopoiesis. Blood. 2003;102:2074-80 pubmed
  37. Yuan L, Yu W, Yuan Z, Haudenschild C, Qu C. Role of SHP-2 tyrosine phosphatase in the DNA damage-induced cell death response. J Biol Chem. 2003;278:15208-16 pubmed
    ..These results together suggest a novel nuclear function for SHP-2 phosphatase in the regulation of DNA damage-induced apoptotic responses. ..
  38. Banno R, Zimmer D, De Jonghe B, Atienza M, Rak K, Yang W, et al. PTP1B and SHP2 in POMC neurons reciprocally regulate energy balance in mice. J Clin Invest. 2010;120:720-34 pubmed publisher
    Protein tyrosine phosphatase 1B (PTP1B) and SH2 domain-containing protein tyrosine phosphatase-2 (SHP2) have been shown in mice to regulate metabolism via the central nervous system, but the specific neurons mediating these effects are ..
  39. Zhao R, Fu X, Teng L, Li Q, Zhao Z. Blocking the function of tyrosine phosphatase SHP-2 by targeting its Src homology 2 domains. J Biol Chem. 2003;278:42893-8 pubmed
    ..This study thus provides a novel and highly specific method to interrupt the function of SHP-2 in cells. ..
  40. Kharitonenkov A, Chen Z, Sures I, Wang H, Schilling J, Ullrich A. A family of proteins that inhibit signalling through tyrosine kinase receptors. Nature. 1997;386:181-6 pubmed
    ..Our findings indicate that proteins belonging to the SIRP family generally regulate signals defining different physiological and pathological processes. ..
  41. De Rocca Serra Nédélec A, Edouard T, Tréguer K, Tajan M, Araki T, Dance M, et al. Noonan syndrome-causing SHP2 mutants inhibit insulin-like growth factor 1 release via growth hormone-induced ERK hyperactivation, which contributes to short stature. Proc Natl Acad Sci U S A. 2012;109:4257-62 pubmed publisher
    ..syndrome (NS), a genetic disease caused in half of cases by activating mutations of the tyrosine phosphatase SHP2 (PTPN11), is characterized by congenital cardiopathies, facial dysmorphic features, and short stature...
  42. Xu D, Liu X, Yu W, Meyerson H, Guo C, Gerson S, et al. Non-lineage/stage-restricted effects of a gain-of-function mutation in tyrosine phosphatase Ptpn11 (Shp2) on malignant transformation of hematopoietic cells. J Exp Med. 2011;208:1977-88 pubmed publisher
    Activating mutations in protein tyrosine phosphatase 11 (Ptpn11) have been identified in childhood acute leukemias, in addition to juvenile myelomonocytic leukemia (JMML), which is a myeloproliferative disorder (MPD)...
  43. Yu W, Hawley T, Hawley R, Qu C. Catalytic-dependent and -independent roles of SHP-2 tyrosine phosphatase in interleukin-3 signaling. Oncogene. 2003;22:5995-6004 pubmed
    ..Taken together, these results suggest that SHP-2 tyrosine phosphatase plays multiple roles in IL-3 signal transduction, functioning in both catalytic-dependent and -independent manners in the Jak/Stat, Erk, and PI3 kinase pathways. ..
  44. Agazie Y, Movilla N, Ischenko I, Hayman M. The phosphotyrosine phosphatase SHP2 is a critical mediator of transformation induced by the oncogenic fibroblast growth factor receptor 3. Oncogene. 2003;22:6909-18 pubmed
    ..The Src homology 2 domain-containing phosphotyrosine phosphatase (SHP2) is a critical mediator of RTK signaling, but its role in oncogenic RTK-induced cell transformation and cancer ..
  45. Qu C, Shi Z, Shen R, Tsai F, Orkin S, Feng G. A deletion mutation in the SH2-N domain of Shp-2 severely suppresses hematopoietic cell development. Mol Cell Biol. 1997;17:5499-507 pubmed
    ..The in vitro ES cell differentiation assay can be used as a biological tool in dissecting cytoplasmic signaling pathways. ..
  46. Zhang S, Tsiaras W, Araki T, Wen G, Minichiello L, Klein R, et al. Receptor-specific regulation of phosphatidylinositol 3'-kinase activation by the protein tyrosine phosphatase Shp2. Mol Cell Biol. 2002;22:4062-72 pubmed
    ..We have found that the protein tyrosine phosphatase Shp2 regulates the strength and duration of phosphatidylinositol 3'-kinase (PI3K) activation in the epidermal growth ..
  47. Dong X, Li X, Gao T, Zhang E, Feng G, Xiong W, et al. Shp2 is dispensable in the formation and maintenance of the neuromuscular junction. Neurosignals. 2006;15:53-63 pubmed
    b>SHP2, a protein tyrosine phosphatase with two SH2 domains, has been implicated in regulating acetylcholine receptor (AChR) gene expression and cluster formation in cultured muscle cells...
  48. Huber M, Izzi L, Grondin P, Houde C, Kunath T, Veillette A, et al. 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. J Biol Chem. 1999;274:335-44 pubmed
    ..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. ..
  49. Salmond R, Huyer G, Kotsoni A, Clements L, Alexander D. The src homology 2 domain-containing tyrosine phosphatase 2 regulates primary T-dependent immune responses and Th cell differentiation. J Immunol. 2005;175:6498-508 pubmed
    The src homology 2 domain-containing tyrosine phosphatase 2 (SHP2) plays an important role in development and in growth factor receptor signaling pathways, yet little is known of its role in the immune system...
  50. Mohi M, Williams I, Dearolf C, Chan G, Kutok J, Cohen S, et al. Prognostic, therapeutic, and mechanistic implications of a mouse model of leukemia evoked by Shp2 (PTPN11) mutations. Cancer Cell. 2005;7:179-91 pubmed
    The SH2-containing tyrosine phosphatase Shp2 (PTPN11) is required for growth factor and cytokine signaling...
  51. Hagihara K, Zhang E, Ke Y, Liu G, Liu J, Rao Y, et al. Shp2 acts downstream of SDF-1alpha/CXCR4 in guiding granule cell migration during cerebellar development. Dev Biol. 2009;334:276-84 pubmed publisher
    b>Shp2 is a non-receptor protein tyrosine phosphatase containing two Src homology 2 (SH2) domains that is implicated in intracellular signaling events controlling cell proliferation, differentiation and migration...
  52. Jack G, Zhang L, Friedman A. M-CSF elevates c-Fos and phospho-C/EBPalpha(S21) via ERK whereas G-CSF stimulates SHP2 phosphorylation in marrow progenitors to contribute to myeloid lineage specification. Blood. 2009;114:2172-80 pubmed publisher
    ..transducer and activator of transcription 3 and induced Src homology region 2 domain-containing phosphatase 2 (SHP2) phosphorylation, whereas M-CSF preferentially activated phospholipase Cgamma2, and thereby extracellular signal-..
  53. Araki T, Mohi M, Ismat F, Bronson R, Williams I, Kutok J, et al. Mouse model of Noonan syndrome reveals cell type- and gene dosage-dependent effects of Ptpn11 mutation. Nat Med. 2004;10:849-57 pubmed
    ..Mutations of Ptpn11 (also known as Shp2), which encodes the protein-tyrosine phosphatase Shp2, occur in approximately 50% of ..
  54. Zhang W, Chan R, Chen H, Yang Z, He Y, Zhang X, et al. Negative regulation of Stat3 by activating PTPN11 mutants contributes to the pathogenesis of Noonan syndrome and juvenile myelomonocytic leukemia. J Biol Chem. 2009;284:22353-63 pubmed publisher
    ..Approximately 50% of NS patients have germline gain-of-function mutations in PTPN11, which encodes the protein-tyrosine phosphatase, Shp2...
  55. Futami M, Zhu Q, Whichard Z, Xia L, Ke Y, Neel B, et al. G-CSF receptor activation of the Src kinase Lyn is mediated by Gab2 recruitment of the Shp2 phosphatase. Blood. 2011;118:1077-86 pubmed publisher
    ..factor (G-CSF) activates Lyn, the predominant Src kinase in myeloid cells, through Gab2-mediated recruitment of Shp2. After G-CSF stimulation, Lyn dynamically associates with Gab2 in a spatiotemporal manner...
  56. Bard Chapeau E, Yuan J, Droin N, Long S, Zhang E, Nguyen T, et al. Concerted functions of Gab1 and Shp2 in liver regeneration and hepatoprotection. Mol Cell Biol. 2006;26:4664-74 pubmed
    ..We show here that association of Gab1 adaptor protein and Shp2 tyrosine phosphatase is a critical event at the early phase of liver regeneration...
  57. Chan G, Kalaitzidis D, Usenko T, Kutok J, Yang W, Mohi M, et al. Leukemogenic Ptpn11 causes fatal myeloproliferative disorder via cell-autonomous effects on multiple stages of hematopoiesis. Blood. 2009;113:4414-24 pubmed publisher
    b>PTPN11, which encodes the tyrosine phosphatase SHP2, is mutated in approximately 35% of patients with juvenile myelomonocytic leukemia (JMML) and at a lower incidence in other neoplasms...
  58. Kim H, Feng G, Chen D, King P, Kamiya N. Targeted disruption of Shp2 in chondrocytes leads to metachondromatosis with multiple cartilaginous protrusions. J Bone Miner Res. 2014;29:761-9 pubmed publisher
    ..Recently, it has been reported that loss-of-function mutations of the SHP2 gene, which encodes the SHP2 protein tyrosine phosphatase, are associated with metachondromatosis...
  59. Yang W, Wang J, Moore D, Liang H, Dooner M, Wu Q, et al. Ptpn11 deletion in a novel progenitor causes metachondromatosis by inducing hedgehog signalling. Nature. 2013;499:491-5 pubmed publisher
    The tyrosine phosphatase SHP2, encoded by PTPN11, is required for the survival, proliferation and differentiation of various cell types...
  60. Lu W, Gong D, Bar Sagi D, Cole P. Site-specific incorporation of a phosphotyrosine mimetic reveals a role for tyrosine phosphorylation of SHP-2 in cell signaling. Mol Cell. 2001;8:759-69 pubmed
    ..These studies support a novel mechanism explaining how tyrosine phosphorylation of a PTPase is important in signal transduction. ..
  61. Kim H, Aruwajoye O, Sucato D, Richards B, Feng G, Chen D, et al. Induction of SHP2 deficiency in chondrocytes causes severe scoliosis and kyphosis in mice. Spine (Phila Pa 1976). 2013;38:E1307-12 pubmed publisher
    ..Genetic engineering techniques were used to develop an animal model of juvenile scoliosis during a postnatal skeletal-growth stage...
  62. Wu X, Guo W, Wu L, Gu Y, Gu L, Xu S, et al. Selective sequestration of STAT1 in the cytoplasm via phosphorylated SHP-2 ameliorates murine experimental colitis. J Immunol. 2012;189:3497-507 pubmed
    ..These findings could lead to increased options for the treatment of Crohn's disease and other Th1-mediated inflammatory diseases. ..
  63. Mali R, Ma P, Zeng L, Martin H, Ramdas B, He Y, et al. Role of SHP2 phosphatase in KIT-induced transformation: identification of SHP2 as a druggable target in diseases involving oncogenic KIT. Blood. 2012;120:2669-78 pubmed
    ..We show that SHP2 phosphatase is essential for oncogenic KIT-induced growth and survival in vitro and myeloproliferative disease (MPD)..
  64. Sharma N, Kumar V, Everingham S, Mali R, Kapur R, Zeng L, et al. SH2 domain-containing phosphatase 2 is a critical regulator of connective tissue mast cell survival and homeostasis in mice. Mol Cell Biol. 2012;32:2653-63 pubmed publisher
    ..Here, we report that SH2 domain-containing phosphatase 2 (SHP2) signaling downstream of KIT is essential for mast cell survival and homeostasis in mice...
  65. Bettaieb A, Matsuo K, Matsuo I, Nagata N, Chahed S, Liu S, et al. Adipose-specific deletion of Src homology phosphatase 2 does not significantly alter systemic glucose homeostasis. Metabolism. 2011;60:1193-201 pubmed publisher
    The SH2 domain-containing protein-tyrosine phosphatase Src homology phosphatase 2 (Shp2) has been implicated in a variety of growth factor signaling pathways, but its metabolic role in some peripheral insulin-responsive tissues remains ..
  66. Montagner A, Yart A, Dance M, Perret B, Salles J, Raynal P. A novel role for Gab1 and SHP2 in epidermal growth factor-induced Ras activation. J Biol Chem. 2005;280:5350-60 pubmed
    b>SHP2 was recently found to down-regulate PI3K activation by dephosphorylating Gab1 but the mechanisms explaining the positive role of the Gab1/SHP2 pathway in EGF-induced Ras activation remain ill defined...
  67. Grossmann K, Wende H, Paul F, Cheret C, Garratt A, Zurborg S, et al. The tyrosine phosphatase Shp2 (PTPN11) directs Neuregulin-1/ErbB signaling throughout Schwann cell development. Proc Natl Acad Sci U S A. 2009;106:16704-9 pubmed publisher
    The nonreceptor tyrosine phosphatase Shp2 (PTPN11) has been implicated in tyrosine kinase, cytokine, and integrin receptor signaling...
  68. Zhang S, Hao E, Yu J, Liu W, Wang J, Levine F, et al. Coordinated regulation by Shp2 tyrosine phosphatase of signaling events controlling insulin biosynthesis in pancreatic beta-cells. Proc Natl Acad Sci U S A. 2009;106:7531-6 pubmed publisher
    ..Mice with conditional ablation of the Shp2/Ptpn11 gene in the pancreas exhibited defective glucose-stimulated insulin secretion and impaired glucose tolerance...
  69. Qu C, Yu W, Azzarelli B, Feng G. Genetic evidence that Shp-2 tyrosine phosphatase is a signal enhancer of the epidermal growth factor receptor in mammals. Proc Natl Acad Sci U S A. 1999;96:8528-33 pubmed
    ..Thus, we provide biological evidence here that protein-tyrosine phosphatase Shp-2 acts to enhance information flow from the EGF-R in mouse growth and development. ..
  70. Kontaridis M, Liu X, Zhang L, Bennett A. Role of SHP-2 in fibroblast growth factor receptor-mediated suppression of myogenesis in C2C12 myoblasts. Mol Cell Biol. 2002;22:3875-91 pubmed
    ..We propose that SHP-2 plays a pivotal role in FGFR signaling in myoblasts via both Erk-dependent and Erk-independent pathways. ..
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    ..The increased sympathetic innervation in target tissues of neurons expressing mutant SHP-2 may result from interference with normal "stop" signals dependent on signaling by gradients of NGF. ..