Gene Symbol: Ptpn6
Description: protein tyrosine phosphatase, non-receptor type 6
Alias: Ptph6, Shp-1, tyrosine-protein phosphatase non-receptor type 6, SH2 phosphatase 1, protein-tyrosine phosphatase SHP-1
Species: rat
Products:     Ptpn6

Top Publications

  1. 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. ..
  2. Sarmiento N, Sánchez Bernal C, Ayra M, Perez N, Hernández Hernández A, Calvo J, et al. Changes in the expression and dynamics of SHP-1 and SHP-2 during cerulein-induced acute pancreatitis in rats. Biochim Biophys Acta. 2008;1782:271-9 pubmed publisher
    ..Finally, both JNK and ERK1/2 and intracellular cAMP levels are able to modulate the expression of these PTPs. ..
  3. Pani G, Fischer K, Mlinaric Rascan I, Siminovitch K. Signaling capacity of the T cell antigen receptor is negatively regulated by the PTP1C tyrosine phosphatase. J Exp Med. 1996;184:839-52 pubmed
  4. García Hernández V, Sarmiento N, Sánchez Bernal C, Matellán L, Calvo J, Sánchez Yagüe J. Modulation in the expression of SHP-1, SHP-2 and PTP1B due to the inhibition of MAPKs, cAMP and neutrophils early on in the development of cerulein-induced acute pancreatitis in rats. Biochim Biophys Acta. 2014;1842:192-201 pubmed publisher
  5. Mori Y, Tsuji S, Inui M, Sakamoto Y, Endo S, Ito Y, et al. Inhibitory immunoglobulin-like receptors LILRB and PIR-B negatively regulate osteoclast development. J Immunol. 2008;181:4742-51 pubmed
    ..Modulation of these regulatory receptors may be a novel way to control various skeletal system disorders and inflammatory arthritis. ..
  6. Liu S, Alkema P, Tieche C, Tefft B, Liu D, Li Y, et al. Negative regulation of monocyte adhesion to arterial elastic laminae by signal regulatory protein alpha and Src homology 2 domain-containing protein-tyrosine phosphatase-1. J Biol Chem. 2005;280:39294-301 pubmed
    ..These observations suggest that SIRP alpha and SHP-1 potentially mediate the inhibitory effect of elastic laminae on monocyte adhesion. ..
  7. Feng Y, Sun Y, Douglas J. Gbeta gamma -independent constitutive association of Galpha s with SHP-1 and angiotensin II receptor AT2 is essential in AT2-mediated ITIM-independent activation of SHP-1. Proc Natl Acad Sci U S A. 2002;99:12049-54 pubmed
    ..The AT(2)-mediated ITIM-independent activation of SHP-1 that is distinct from the conventional mode of activation, may represent a general paradigm for activation of SHP-1/2-class tyrosine phosphatases by G protein-coupled receptors. ..
  8. Mima A, Kitada M, Geraldes P, Li Q, Matsumoto M, Mizutani K, et al. Glomerular VEGF resistance induced by PKC?/SHP-1 activation and contribution to diabetic nephropathy. FASEB J. 2012;26:2963-74 pubmed publisher
    ..Hyperglycemia and diabetes can cause glomerular podocyte apoptosis and endothelial dysfunction partly due to increased PKC?/p38 MAPK activation and the expression of SHP-1 to cause VEGF resistance, independent of NF-?B activation. ..
  9. Alvarez S, Seguin L, Villarreal R, Nahmias C, Ciuffo G. Involvement of c-Src tyrosine kinase in SHP-1 phosphatase activation by Ang II AT2 receptors in rat fetal tissues. J Cell Biochem. 2008;105:703-11 pubmed publisher
    ..Thus, we clearly establish that SHP-1 activation, mediated by the AT(2) subtype, involves c-Src and precedes protein tyrosine dephosphorylation, in rat fetal membranes. ..

More Information


  1. Valentino L, Pierre J. JAK/STAT signal transduction: regulators and implication in hematological malignancies. Biochem Pharmacol. 2006;71:713-21 pubmed
    ..Furthermore, silencing of socs-1 and shp-1 expression by gene methylation is observed in some cancer cells. ..
  2. Incoronato M, D Alessio A, Paladino S, Zurzolo C, Carlomagno M, Cerchia L, et al. The Shp-1 and Shp-2, tyrosine phosphatases, are recruited on cell membrane in two distinct molecular complexes including Ret oncogenes. Cell Signal. 2004;16:847-56 pubmed
    ..Our results well support the evidence that Ret complexes within and outside rafts mediate distinct biological functions, and indicate that the presence of either Shps participates to determine such functions. ..
  3. Mazharian A, Mori J, Wang Y, Heising S, Neel B, Watson S, et al. Megakaryocyte-specific deletion of the protein-tyrosine phosphatases Shp1 and Shp2 causes abnormal megakaryocyte development, platelet production, and function. Blood. 2013;121:4205-20 pubmed publisher
    ..This study establishes Shp1 and Shp2 as major regulators of megakaryocyte development, platelet production, and function. ..
  4. Zhu Z, Li R, Li H, Zhou T, Davis R. FCRL5 exerts binary and compartment-specific influence on innate-like B-cell receptor signaling. Proc Natl Acad Sci U S A. 2013;110:E1282-90 pubmed publisher
    ..These findings collectively imply a specialized counterregulatory role for FCRL molecules at the intersection of innate and adaptive immunity. ..
  5. Ghalaut P, Mahajan S, Mahajan K, Kumar M. Effect of treatment on pulmonary functions in chronic severe anaemia. Indian J Chest Dis Allied Sci. 1992;34:137-40 pubmed
    ..FEV1, PEFR, RV/TLC were essentially normal. We conclude that the observed changes produced in lung functions during anaemic state are fully reversible after its correction. ..
  6. Jiao H, Berrada K, Yang W, Tabrizi M, Platanias L, Yi T. Direct association with and dephosphorylation of Jak2 kinase by the SH2-domain-containing protein tyrosine phosphatase SHP-1. Mol Cell Biol. 1996;16:6985-92 pubmed
    ..They also suggest that such interactions may provide one of the mechanisms that control SHP-1 substrate specificity. ..
  7. Kitzig F, Martinez Barriocanal A, Lopez Botet M, Sayos J. Cloning of two new splice variants of Siglec-10 and mapping of the interaction between Siglec-10 and SHP-1. Biochem Biophys Res Commun. 2002;296:355-62 pubmed
    ..Finally, we demonstrated that Siglec-10 was not able to bind SAP/SH2d1A, indicating that the so-called CD150-like motif in Siglec-10 might be a docking site for other signal transduction mediators. ..
  8. Westgaard I, Dissen E, Torgersen K, Lazetic S, Lanier L, Phillips J, et al. The lectin-like receptor KLRE1 inhibits natural killer cell cytotoxicity. J Exp Med. 2003;197:1551-61 pubmed
    ..Together, our results indicate that KLRE1 may form a functional heterodimer with an as yet unidentified ITIM-bearing partner that recruits SHP-1 to generate an inhibitory receptor complex. ..
  9. Chihara K, Nakashima K, Takeuchi K, Sada K. Association of 3BP2 with SHP-1 regulates SHP-1-mediated production of TNF-? in RBL-2H3 cells. Genes Cells. 2011;16:1133-45 pubmed publisher
    ..These findings suggest that 3BP2 directly interacts with Tyr(564) -phosphorylated form of SHP-1 and positively regulates the function of SHP-1 in Fc?RI-mediated signaling in mast cells. ..
  10. Sugano M, Tsuchida K, Hata T, Makino N. RNA interference targeting SHP-1 attenuates myocardial infarction in rats. FASEB J. 2005;19:2054-6 pubmed
    ..Suppression of SHP-1 with the SHP-1 siRNA vector markedly reduced the infarct size in AMI. ..
  11. Pani G, Siminovitch K, Paige C. The motheaten mutation rescues B cell signaling and development in CD45-deficient mice. J Exp Med. 1997;186:581-8 pubmed
  12. Montano X. Repression of SHP-1 expression by p53 leads to trkA tyrosine phosphorylation and suppression of breast cancer cell proliferation. Oncogene. 2009;28:3787-800 pubmed publisher
    ..These data provide an explanation as to why high trkA levels are associated with favourable prognosis. ..
  13. Kon Kozlowski M, Pani G, Pawson T, Siminovitch K. The tyrosine phosphatase PTP1C associates with Vav, Grb2, and mSos1 in hematopoietic cells. J Biol Chem. 1996;271:3856-62 pubmed
  14. Clark E, Shultz L, Pollack S. Mutations in mice that influence natural killer (NK) cell activity. Immunogenetics. 1981;12:601-13 pubmed
    ..Unlike the obese gene, other mutations leading to obesity, diabetes (db) and yellow (Ay), did not impair NK-cell function. The possible site of gene action of these mutations in the NK-cell pathway is discussed. ..
  15. Xiao X, Zhao X, Xu L, Yue L, Liu F, Cai J, et al. Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats. Pain. 2015;156:597-608 pubmed publisher
  16. Seguin L, Villarreal R, Ciuffo G. AT?receptors recruit c-Src, SHP-1 and FAK upon activation by Ang II in PND15 rat hindbrain. Neurochem Int. 2012;60:199-207 pubmed publisher
    ..In this model, we showed a complex containing AT(2)/SHP-1/c-Src/p85FAK, suggesting a potential role of Ang II AT(2) receptors in cerebellar development and neuronal differentiation. ..
  17. Xu W, Tao H, Liu Y, Jiang C. [The state of SHP-1 and CD45 in lymphocyte under high partial pressure of oxygen]. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2005;21:15-8 pubmed
    ..SHP-1 and CD45 might be one of the key points of action through which high PO2 exerts its effects on lymphocytes. ..
  18. Jones E, Vinh A, McCarthy C, Gaspari T, Widdop R. AT2 receptors: functional relevance in cardiovascular disease. Pharmacol Ther. 2008;120:292-316 pubmed publisher
    ..During cardiovascular disease, there is likely to be an increased functional importance of AT2R, stimulated by Ang II, or even shorter angiotensin peptide fragments, to limit AT1R-mediated overactivity and cardiovascular pathologies. ..
  19. Li J, Mogi M, Tsukuda K, Tomochika H, Iwanami J, Min L, et al. Angiotensin II-induced neural differentiation via angiotensin II type 2 (AT2) receptor-MMS2 cascade involving interaction between AT2 receptor-interacting protein and Src homology 2 domain-containing protein-tyrosine phosphatase 1. Mol Endocrinol. 2007;21:499-511 pubmed
    ..These results provide a new insight into the contribution of AT2 receptor stimulation to neural differentiation via transactivation of MMS2 expression involving the association of ATIP and SHP-1. ..
  20. Phillippe M, Bradley D, Engle D, Sweet L. SHP protein tyrosine phosphatase expression in rat uterine tissue. J Soc Gynecol Investig. 2006;13:338-42 pubmed
  21. Rodríguez Ubreva F, Cariaga Martinez A, Cortes M, Romero De Pablos M, Ropero S, Lopez Ruiz P, et al. Knockdown of protein tyrosine phosphatase SHP-1 inhibits G1/S progression in prostate cancer cells through the regulation of components of the cell-cycle machinery. Oncogene. 2010;29:345-55 pubmed publisher
    ..This study shows that SHP-1 depletion promotes cell-cycle arrest by modulating the activity of cell-cycle regulators and suggests that SHP-1 may be required for the proper functioning of events governing cell-cycle progression. ..
  22. Keilhack H, Muller M, Böhmer S, Frank C, Weidner K, Birchmeier W, et al. Negative regulation of Ros receptor tyrosine kinase signaling. An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1. J Cell Biol. 2001;152:325-34 pubmed
    ..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. ..
  23. Carlyle J, Martin A, Mehra A, Attisano L, Tsui F, Zúñiga Pflücker J. Mouse NKR-P1B, a novel NK1.1 antigen with inhibitory function. J Immunol. 1999;162:5917-23 pubmed
    ..The existence of these two NK1.1 Ags with opposite functions suggests a potential role for NKR-P1 molecules, such as those of the Ly-49 gene family, in regulating NK cell function. ..
  24. Chen Y, Hsieh C, Jayakumar T, Lin K, Chou D, Lu W, et al. Andrographolide induces vascular smooth muscle cell apoptosis through a SHP-1-PP2A-p38MAPK-p53 cascade. Sci Rep. 2014;4:5651 pubmed publisher
    ..These results suggest that andrographolide activates the PP2A-p38MAPK-p53-Bax cascade, causing mitochondrial dysfunction and VSMC death through an SHP-1-dependent mechanism. ..
  25. Shaw S, Bencherif M, Marrero M. Angiotensin II blocks nicotine-mediated neuroprotection against beta-amyloid (1-42) via activation of the tyrosine phosphatase SHP-1. J Neurosci. 2003;23:11224-8 pubmed
    ..These results demonstrate that nicotine-induced tyrosine phosphorylation of JAK2 and neuroprotection against Abeta (1-42) in PC12 cells are blocked by Ang II via AT2 receptor-induced activation of SHP-1. ..
  26. Horvat A, Schwaiger F, Hager G, Brocker F, Streif R, Knyazev P, et al. A novel role for protein tyrosine phosphatase shp1 in controlling glial activation in the normal and injured nervous system. J Neurosci. 2001;21:865-74 pubmed
    ..These results emphasize that SHP1 as a part of different signaling pathways plays an important role in the global regulation of astrocytic and microglial activation in the normal and injured CNS...
  27. Cosman D, Fanger N, Borges L, Kubin M, Chin W, Peterson L, et al. A novel immunoglobulin superfamily receptor for cellular and viral MHC class I molecules. Immunity. 1997;7:273-82 pubmed
    ..Upon tyrosine phosphorylation, LIR-1 associates with the tyrosine phosphatase SHP-1. In contrast to KIRs, LIR-1 is expressed predominantly on monocytic and B lymphoid cell types, suggesting a distinct biological function. ..
  28. Tibaldi E, Zonta F, Bordin L, Magrin E, Gringeri E, Cillo U, et al. The tyrosine phosphatase SHP-1 inhibits proliferation of activated hepatic stellate cells by impairing PDGF receptor signaling. Biochim Biophys Acta. 2014;1843:288-98 pubmed publisher
  29. Denhez B, Lizotte F, Guimond M, Jones N, Takano T, Geraldes P. Increased SHP-1 protein expression by high glucose levels reduces nephrin phosphorylation in podocytes. J Biol Chem. 2015;290:350-8 pubmed publisher
    ..In conclusion, our results demonstrate that high glucose exposure increases SHP-1 interaction with nephrin, causing decreased nephrin phosphorylation, which may, in turn, contribute to diabetic nephropathy. ..
  30. Hoffmann S, Schellack C, Textor S, Konold S, Schmitz D, Cerwenka A, et al. Identification of CLEC12B, an inhibitory receptor on myeloid cells. J Biol Chem. 2007;282:22370-5 pubmed
  31. Zhao J, Lurie D. Loss of SHP-1 phosphatase alters cytokine expression in the mouse hindbrain following cochlear ablation. Cytokine. 2004;28:1-9 pubmed
    ..SHP-1 may therefore play a role in limiting CNS inflammation following injury and disease. ..
  32. Wu L, Iwai M, Li Z, Shiuchi T, Min L, Cui T, et al. Regulation of inhibitory protein-kappaB and monocyte chemoattractant protein-1 by angiotensin II type 2 receptor-activated Src homology protein tyrosine phosphatase-1 in fetal vascular smooth muscle cells. Mol Endocrinol. 2004;18:666-78 pubmed