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Gene Review

PTPN1  -  protein tyrosine phosphatase, non-receptor...

Homo sapiens

Synonyms: PTP-1B, PTP1B, Protein-tyrosine phosphatase 1B, Tyrosine-protein phosphatase non-receptor type 1
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Disease relevance of PTPN1

  • Protein-tyrosine phosphatase-1B negatively regulates insulin signaling in l6 myocytes and Fao hepatoma cells [1].
  • OBJECTIVE: To perform association studies of polymorphisms of the potential candidate essential hypertension (HT) genes GRK4, PTP1B and HSD3B1 [2].
  • Many elements of the PTP1B-IRK interaction are unique to PTP1B, indicating that it may be feasible to generate specific, small molecule inhibitors of this interaction to treat diabetes and obesity [3].
  • Furthermore, PTP-1B-deficient platelets are defective in outside-in alphaIIbbeta3 signaling in vitro as manifested by poor spreading on fibrinogen and decreased clot retraction, and they exhibit ineffective Ca2+ signaling and thrombus formation in vivo [4].
  • Examination of several human breast cancer cell lines with increased c-Src activity showed elevated levels of PTP1B protein relative to normal control breast cells [5].

Psychiatry related information on PTPN1


High impact information on PTPN1


Chemical compound and disease context of PTPN1


Biological context of PTPN1

  • The genetic contribution of PTPN1 to measures of glucose homeostasis has been assessed in 811 Hispanic subjects from the Insulin Resistance Atherosclerosis Study Family Study (IRASFS) [13].
  • We have carried out a detailed association analysis of 23 noncoding SNPs spanning the 161-kb genomic region, which includes the PTPN1 gene [14].
  • Protein tyrosine phosphatase (PTP)-1B, encoded by the PTPN1 gene, inactivates the insulin signal transduction cascade by dephosphorylating phosphotyrosine residues in insulin signaling molecules [15].
  • Recent studies have associated common sequence variants in PTPN1 with type 2 diabetes and diabetes-related phenotypes [15].
  • All of the associated SNPs lie in a single 100-kb haplotype block that encompasses the PTPN1 gene [14].

Anatomical context of PTPN1

  • We studied whether polymorphisms in the PTPN1 gene impact body fat distribution in the HERITAGE Family Study cohort in 502 white and 276 black subjects [16].
  • White subjects with the G82G at the PTPN1 IVS6+G82A polymorphism had higher body fat levels (p = 0.031) and sum of eight skinfolds (p = 0.003) and highest subcutaneous fat on the limbs (p = 0.002) [16].
  • In this study, we have demonstrated that expression of PTP1B is enhanced specifically in various cells expressing p210 bcr-abl, including a cell line derived from a patient with CML [17].
  • In HeLa cells, overexpression of hSPRY2 resulted in an increase in protein-tyrosine phosphatase (PTP1B) amount and activity in the soluble (100,000 x g) fraction of cells without an increase in total amount of cellular PTP1B [18].
  • We investigated the effect of overexpression of protein-tyrosine phosphatase 1B (PTP1B) on insulin signaling in 3T3-L1 adipocytes [19].

Associations of PTPN1 with chemical compounds


Physical interactions of PTPN1


Enzymatic interactions of PTPN1

  • We also show that CLK1 and CLK2 phosphorylate and activate the S. cerevisiae PTP-1B family member, YPTP1 [20].
  • These results suggest that PTP-1B appears not only to interact with and dephosphorylate the insulin-stimulated IR in a perinuclear endosome compartment but is also involved in maintaining the IR in a dephosphorylated state during its biosynthesis [29].

Regulatory relationships of PTPN1


Other interactions of PTPN1


Analytical, diagnostic and therapeutic context of PTPN1


  1. Protein-tyrosine phosphatase-1B negatively regulates insulin signaling in l6 myocytes and Fao hepatoma cells. Egawa, K., Maegawa, H., Shimizu, S., Morino, K., Nishio, Y., Bryer-Ash, M., Cheung, A.T., Kolls, J.K., Kikkawa, R., Kashiwagi, A. J. Biol. Chem. (2001) [Pubmed]
  2. Association of G-protein-coupled receptor kinase 4 haplotypes, but not HSD3B1 or PTP1B polymorphisms, with essential hypertension. Speirs, H.J., Katyk, K., Kumar, N.N., Benjafield, A.V., Wang, W.Y., Morris, B.J. J. Hypertens. (2004) [Pubmed]
  3. Molecular basis for the dephosphorylation of the activation segment of the insulin receptor by protein tyrosine phosphatase 1B. Salmeen, A., Andersen, J.N., Myers, M.P., Tonks, N.K., Barford, D. Mol. Cell (2000) [Pubmed]
  4. PTP-1B is an essential positive regulator of platelet integrin signaling. Arias-Salgado, E.G., Haj, F., Dubois, C., Moran, B., Kasirer-Friede, A., Furie, B.C., Furie, B., Neel, B.G., Shattil, S.J. J. Cell Biol. (2005) [Pubmed]
  5. Identification of protein-tyrosine phosphatase 1B as the major tyrosine phosphatase activity capable of dephosphorylating and activating c-Src in several human breast cancer cell lines. Bjorge, J.D., Pang, A., Fujita, D.J. J. Biol. Chem. (2000) [Pubmed]
  6. Photoperiodic regulation of insulin receptor mRNA and intracellular insulin signaling in the arcuate nucleus of the Siberian hamster, Phodopus sungorus. Tups, A., Helwig, M., Stöhr, S., Barrett, P., Mercer, J.G., Klingenspor, M. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2006) [Pubmed]
  7. The nontransmembrane tyrosine phosphatase PTP-1B localizes to the endoplasmic reticulum via its 35 amino acid C-terminal sequence. Frangioni, J.V., Beahm, P.H., Shifrin, V., Jost, C.A., Neel, B.G. Cell (1992) [Pubmed]
  8. Oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B. van Montfort, R.L., Congreve, M., Tisi, D., Carr, R., Jhoti, H. Nature (2003) [Pubmed]
  9. Suramin derivatives as inhibitors and activators of protein-tyrosine phosphatases. McCain, D.F., Wu, L., Nickel, P., Kassack, M.U., Kreimeyer, A., Gagliardi, A., Collins, D.C., Zhang, Z.Y. J. Biol. Chem. (2004) [Pubmed]
  10. Intestinal Insulin Resistance and Aberrant Production of Apolipoprotein B48 Lipoproteins in an Animal Model of Insulin Resistance and Metabolic Dyslipidemia: Evidence for Activation of Protein Tyrosine Phosphatase-1B, Extracellular Signal-Related Kinase, and Sterol Regulatory Element-Binding Protein-1c in the Fructose-Fed Hamster Intestine. Federico, L.M., Naples, M., Taylor, D., Adeli, K. Diabetes (2006) [Pubmed]
  11. Protein-Tyrosine Phosphatase 1B-Deficient Myocytes Show Increased Insulin Sensitivity and Protection Against Tumor Necrosis Factor-{alpha}-Induced Insulin Resistance. Nieto-Vazquez, I., Fernández-Veledo, S., de Alvaro, C., Rondinone, C.M., Valverde, A.M., Lorenzo, M. Diabetes (2007) [Pubmed]
  12. Crystal structure of Yersinia protein tyrosine phosphatase at 2.5 A and the complex with tungstate. Stuckey, J.A., Schubert, H.L., Fauman, E.B., Zhang, Z.Y., Dixon, J.E., Saper, M.A. Nature (1994) [Pubmed]
  13. Association of protein tyrosine phosphatase 1B gene polymorphisms with measures of glucose homeostasis in Hispanic Americans: the insulin resistance atherosclerosis study (IRAS) family study. Palmer, N.D., Bento, J.L., Mychaleckyj, J.C., Langefeld, C.D., Campbell, J.K., Norris, J.M., Haffner, S.M., Bergman, R.N., Bowden, D.W. Diabetes (2004) [Pubmed]
  14. Association of protein tyrosine phosphatase 1B gene polymorphisms with type 2 diabetes. Bento, J.L., Palmer, N.D., Mychaleckyj, J.C., Lange, L.A., Langefeld, C.D., Rich, S.S., Freedman, B.I., Bowden, D.W. Diabetes (2004) [Pubmed]
  15. Association testing of the protein tyrosine phosphatase 1B gene (PTPN1) with type 2 diabetes in 7,883 people. Florez, J.C., Agapakis, C.M., Burtt, N.P., Sun, M., Almgren, P., Råstam, L., Tuomi, T., Gaudet, D., Hudson, T.J., Daly, M.J., Ardlie, K.G., Hirschhorn, J.N., Groop, L., Altshuler, D. Diabetes (2005) [Pubmed]
  16. Protein tyrosine phosphatase 1B variant associated with fat distribution and insulin metabolism. Ukkola, O., Rankinen, T., Lakka, T., Leon, A.S., Skinner, J.S., Wilmore, J.H., Rao, D.C., Kesäniemi, Y.A., Bouchard, C. Obes. Res. (2005) [Pubmed]
  17. Protein tyrosine phosphatase 1B antagonizes signalling by oncoprotein tyrosine kinase p210 bcr-abl in vivo. LaMontagne, K.R., Flint, A.J., Franza, B.R., Pandergast, A.M., Tonks, N.K. Mol. Cell. Biol. (1998) [Pubmed]
  18. Protein-tyrosine phosphatase-1B (PTP1B) mediates the anti-migratory actions of Sprouty. Yigzaw, Y., Poppleton, H.M., Sreejayan, N., Hassid, A., Patel, T.B. J. Biol. Chem. (2003) [Pubmed]
  19. Mechanism for differential effect of protein-tyrosine phosphatase 1B on Akt versus mitogen-activated protein kinase in 3T3-L1 adipocytes. Shimizu, S., Maegawa, H., Egawa, K., Shi, K., Bryer-Ash, M., Kashiwagi, A. Endocrinology (2002) [Pubmed]
  20. The CLK family kinases, CLK1 and CLK2, phosphorylate and activate the tyrosine phosphatase, PTP-1B. Moeslein, F.M., Myers, M.P., Landreth, G.E. J. Biol. Chem. (1999) [Pubmed]
  21. Tyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B. Possible facilitation by the formation of a ternary complex with the Grb2 adaptor protein. Goldstein, B.J., Bittner-Kowalczyk, A., White, M.F., Harbeck, M. J. Biol. Chem. (2000) [Pubmed]
  22. Regulation of protein tyrosine phosphatase 1B in intact cells by S-nitrosothiols. Li, S., Whorton, A.R. Arch. Biochem. Biophys. (2003) [Pubmed]
  23. Tyrosine phosphatase PTP1B interacts with TRPV6 in vivo and plays a role in TRPV6-mediated calcium influx in HEK293 cells. Sternfeld, L., Krause, E., Schmid, A., Anderie, I., Latas, A., Al-Shaldi, H., Köhl, A., Evers, K., Hofer, H.W., Schulz, I. Cell. Signal. (2005) [Pubmed]
  24. Purification and characterization of T cell protein tyrosine phosphatase reveals significant functional homology to protein tyrosine phosphatase-1B. Romsicki, Y., Kennedy, B.P., Asante-Appiah, E. Arch. Biochem. Biophys. (2003) [Pubmed]
  25. Protein-tyrosine phosphatase 1B complexes with the insulin receptor in vivo and is tyrosine-phosphorylated in the presence of insulin. Bandyopadhyay, D., Kusari, A., Kenner, K.A., Liu, F., Chernoff, J., Gustafson, T.A., Kusari, J. J. Biol. Chem. (1997) [Pubmed]
  26. PTP1B modulates the association of beta-catenin with N-cadherin through binding to an adjacent and partially overlapping target site. Xu, G., Arregui, C., Lilien, J., Balsamo, J. J. Biol. Chem. (2002) [Pubmed]
  27. Phosphorylated alpha-actinin and protein-tyrosine phosphatase 1B coregulate the disassembly of the focal adhesion kinase x Src complex and promote cell migration. Zhang, Z., Lin, S.Y., Neel, B.G., Haimovich, B. J. Biol. Chem. (2006) [Pubmed]
  28. PTP1B regulates cortactin tyrosine phosphorylation by targeting Tyr446. Stuible, M., Dubé, N., Tremblay, M.L. J. Biol. Chem. (2008) [Pubmed]
  29. Protein tyrosine phosphatase-1B dephosphorylation of the insulin receptor occurs in a perinuclear endosome compartment in human embryonic kidney 293 cells. Romsicki, Y., Reece, M., Gauthier, J.Y., Asante-Appiah, E., Kennedy, B.P. J. Biol. Chem. (2004) [Pubmed]
  30. Protein tyrosine phosphatase 1B interacts with and is tyrosine phosphorylated by the epidermal growth factor receptor. Liu, F., Chernoff, J. Biochem. J. (1997) [Pubmed]
  31. The tyrosine phosphatase 1B regulates linker for activation of T-cell phosphorylation and platelet aggregation upon FcgammaRIIa cross-linking. Ragab, A., Bodin, S., Viala, C., Chap, H., Payrastre, B., Ragab-Thomas, J. J. Biol. Chem. (2003) [Pubmed]
  32. Turn-off, drop-out: functional state switching of cadherins. Lilien, J., Balsamo, J., Arregui, C., Xu, G. Dev. Dyn. (2002) [Pubmed]
  33. Monitoring the activation state of the insulin-like growth factor-1 receptor and its interaction with protein tyrosine phosphatase 1B using bioluminescence resonance energy transfer. Blanquart, C., Boute, N., Lacasa, D., Issad, T. Mol. Pharmacol. (2005) [Pubmed]
  34. Multi-site phosphorylation of the protein tyrosine phosphatase, PTP1B: identification of cell cycle regulated and phorbol ester stimulated sites of phosphorylation. Flint, A.J., Gebbink, M.F., Franza, B.R., Hill, D.E., Tonks, N.K. EMBO J. (1993) [Pubmed]
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