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Gene Review

Ptpn1  -  protein tyrosine phosphatase, non-receptor...

Mus musculus

Synonyms: PTP-1B, PTP-HA2, PTP1B, Protein-tyrosine phosphatase 1B, Protein-tyrosine phosphatase HA2, ...
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Disease relevance of Ptpn1

  • Previous studies indicated that PTP1B is overexpressed in a significant subset of breast and ovarian cancers, especially in those overexpressing HER2/Neu (HER2(+) tumors) [1].
  • Although heterozygous loss of PTP1B has no effect on tumorigenesis, homozygous PTP1B deficiency dramatically delays or prevents the onset of MMTV-NeuNT-evoked breast tumors [1].
  • To determine how PTP1B deficiency affects HER2-evoked breast tumorigenesis, we generated mouse mammary tumor virus (MMTV)-NeuNT transgenic mice lacking one or both alleles of PTP1B [1].
  • Overexpression of PTP1B protein has been observed in insulin-resistant states associated with obesity [2].
  • Mice lacking a functional PTP1B gene exhibit increased insulin sensitivity and are resistant to weight gain [2].
  • This report provides a rationale for the development of PTP1B as a new therapeutic target in breast cancer [3].

High impact information on Ptpn1


Chemical compound and disease context of Ptpn1

  • Mice lacking the tyrosine phosphatase PTP1B are protected from diet-induced obesity and are hypersensitive to leptin, but the site and mechanism for these effects remain controversial [4].
  • Activation of Galpha(i2) in mouse adipocytes with lysophosphatidic acid was shown to decrease PTP1B activity, whereas pertussis toxin inactivates Galpha(i2), blocks lysophosphatidic acid-stimulated inhibition of PTP1B activity, and blocks tonic suppression of PTP1B activity by Galpha(i2) [6].
  • Gold thioglucose treatment, which ablates leptin-responsive hypothalamic neurons, partially overcomes resistance to obesity in PTP1B(-/-) mice [7].
  • Wild-type mice treated with TNF-alpha developed a pronounced hyperglycemia along the glucose tolerance test, accompanied by an impaired insulin signaling and increased PTP1B activity in muscle [8].
  • In summary, microarray results suggest that reduction of PTP1B may alleviate hyperglycemia and enhance insulin sensitivity by a different mechanism than TZD treatment [9].

Biological context of Ptpn1


Anatomical context of Ptpn1

  • Experiments using PTP1B(-/-) fibroblast lines, dominant-negative mutants, or small interfering RNAs indicate that PTP1B contributes to dephosphorylation of the epidermal growth factor receptor and platelet-derived growth factor receptors as well [1].
  • The effects of PTP1B deficiency correlate with defective extracellular signal-regulated kinase activation in preneoplastic mammary glands from compound mutant mice [1].
  • In adipose tissue and muscle of obese humans and rodents, PTP1B expression is increased, which led to the hypothesis that PTP1B plays a role in the pathogenesis of insulin resistance [13].
  • Immortalized neonatal hepatocytes and primary neonatal and adult hepatocytes have been generated from PTP1B(-/-) and wild-type mice [11].
  • PTP1B protein and mRNA were reduced in liver and fat with no effect in skeletal muscle [14].

Associations of Ptpn1 with chemical compounds


Physical interactions of Ptpn1


Enzymatic interactions of Ptpn1

  • A cytosolic protein-tyrosine phosphatase PTP1B specifically dephosphorylates and deactivates prolactin-activated STAT5a and STAT5b [23].

Regulatory relationships of Ptpn1


Other interactions of Ptpn1


Analytical, diagnostic and therapeutic context of Ptpn1


  1. Protein-tyrosine phosphatase 1B is required for HER2/Neu-induced breast cancer. Bentires-Alj, M., Neel, B.G. Cancer Res. (2007) [Pubmed]
  2. Protein tyrosine phosphatase 1B reduction regulates adiposity and expression of genes involved in lipogenesis. Rondinone, C.M., Trevillyan, J.M., Clampit, J., Gum, R.J., Berg, C., Kroeger, P., Frost, L., Zinker, B.A., Reilly, R., Ulrich, R., Butler, M., Monia, B.P., Jirousek, M.R., Waring, J.F. Diabetes (2002) [Pubmed]
  3. Protein tyrosine phosphatase 1B deficiency or inhibition delays ErbB2-induced mammary tumorigenesis and protects from lung metastasis. Julien, S.G., Dubé, N., Read, M., Penney, J., Paquet, M., Han, Y., Kennedy, B.P., Muller, W.J., Tremblay, M.L. Nat. Genet. (2007) [Pubmed]
  4. Neuronal PTP1B regulates body weight, adiposity and leptin action. Bence, K.K., Delibegovic, M., Xue, B., Gorgun, C.Z., Hotamisligil, G.S., Neel, B.G., Kahn, B.B. Nat. Med. (2006) [Pubmed]
  5. Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Elchebly, M., Payette, P., Michaliszyn, E., Cromlish, W., Collins, S., Loy, A.L., Normandin, D., Cheng, A., Himms-Hagen, J., Chan, C.C., Ramachandran, C., Gresser, M.J., Tremblay, M.L., Kennedy, B.P. Science (1999) [Pubmed]
  6. Galpha(i2) enhances insulin signaling via suppression of protein-tyrosine phosphatase 1B. Tao, J., Malbon, C.C., Wang, H.Y. J. Biol. Chem. (2001) [Pubmed]
  7. PTP1B regulates leptin signal transduction in vivo. Zabolotny, J.M., Bence-Hanulec, K.K., Stricker-Krongrad, A., Haj, F., Wang, Y., Minokoshi, Y., Kim, Y.B., Elmquist, J.K., Tartaglia, L.A., Kahn, B.B., Neel, B.G. Dev. Cell (2002) [Pubmed]
  8. 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]
  9. PTP1B antisense-treated mice show regulation of genes involved in lipogenesis in liver and fat. Waring, J.F., Ciurlionis, R., Clampit, J.E., Morgan, S., Gum, R.J., Jolly, R.A., Kroeger, P., Frost, L., Trevillyan, J., Zinker, B.A., Jirousek, M., Ulrich, R.G., Rondinone, C.M. Mol. Cell. Endocrinol. (2003) [Pubmed]
  10. Liver X receptor agonists ameliorate TNFalpha-induced insulin resistance in murine brown adipocytes by downregulating protein tyrosine phosphatase-1B gene expression. Fern??ndez-Veledo, S., Nieto-Vazquez, I., Rondinone, C.M., Lorenzo, M. Diabetologia (2006) [Pubmed]
  11. Developmental switch from prolonged insulin action to increased insulin sensitivity in protein tyrosine phosphatase 1B-deficient hepatocytes. Gonzalez-Rodriguez, A., Clampit, J.E., Escribano, O., Benito, M., Rondinone, C.M., Valverde, A.M. Endocrinology (2007) [Pubmed]
  12. Effects of small interference RNA against PTP1B and TCPTP on insulin signaling pathway in mouse liver: Evidence for non-synergetic cooperation. Xu, J., Li, L., Hong, J., Huang, W. Cell Biol. Int. (2007) [Pubmed]
  13. Overexpression of protein-tyrosine phosphatase-1B in adipocytes inhibits insulin-stimulated phosphoinositide 3-kinase activity without altering glucose transport or Akt/Protein kinase B activation. Venable, C.L., Frevert, E.U., Kim, Y.B., Fischer, B.M., Kamatkar, S., Neel, B.G., Kahn, B.B. J. Biol. Chem. (2000) [Pubmed]
  14. PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice. Zinker, B.A., Rondinone, C.M., Trevillyan, J.M., Gum, R.J., Clampit, J.E., Waring, J.F., Xie, N., Wilcox, D., Jacobson, P., Frost, L., Kroeger, P.E., Reilly, R.M., Koterski, S., Opgenorth, T.J., Ulrich, R.G., Crosby, S., Butler, M., Murray, S.F., McKay, R.A., Bhanot, S., Monia, B.P., Jirousek, M.R. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  15. Islet-sparing effects of protein tyrosine phosphatase-1b deficiency delays onset of diabetes in IRS2 knockout mice. Kushner, J.A., Haj, F.G., Klaman, L.D., Dow, M.A., Kahn, B.B., Neel, B.G., White, M.F. Diabetes (2004) [Pubmed]
  16. Discovery and structure-activity relationship of oxalylarylaminobenzoic acids as inhibitors of protein tyrosine phosphatase 1B. Liu, G., Szczepankiewicz, B.G., Pei, Z., Janowick, D.A., Xin, Z., Hajduk, P.J., Abad-Zapatero, C., Liang, H., Hutchins, C.W., Fesik, S.W., Ballaron, S.J., Stashko, M.A., Lubben, T., Mika, A.K., Zinker, B.A., Trevillyan, J.M., Jirousek, M.R. J. Med. Chem. (2003) [Pubmed]
  17. The Role of the C-terminal Domain of Protein Tyrosine Phosphatase-1B in Phosphatase Activity and Substrate Binding. Picha, K.M., Patel, S.S., Mandiyan, S., Koehn, J., Wennogle, L.P. J. Biol. Chem. (2007) [Pubmed]
  18. Sodium stibogluconate is a potent inhibitor of protein tyrosine phosphatases and augments cytokine responses in hemopoietic cell lines. Pathak, M.K., Yi, T. J. Immunol. (2001) [Pubmed]
  19. Improved glucose homeostasis in mice with muscle-specific deletion of protein-tyrosine phosphatase 1B. Delibegovic, M., Bence, K.K., Mody, N., Hong, E.G., Ko, H.J., Kim, J.K., Kahn, B.B., Neel, B.G. Mol. Cell. Biol. (2007) [Pubmed]
  20. Basal activation of p70S6K results in adipose-specific insulin resistance in protein-tyrosine phosphatase 1B -/- mice. Ruffolo, S.C., Forsell, P.K., Yuan, X., Desmarais, S., Himms-Hagen, J., Cromlish, W., Wong, K.K., Kennedy, B.P. J. Biol. Chem. (2007) [Pubmed]
  21. Impaired integrin-mediated adhesion and signaling in fibroblasts expressing a dominant-negative mutant PTP1B. Arregui, C.O., Balsamo, J., Lilien, J. J. Cell Biol. (1998) [Pubmed]
  22. Essential tyrosine residues for interaction of the non-receptor protein-tyrosine phosphatase PTP1B with N-cadherin. Rhee, J., Lilien, J., Balsamo, J. J. Biol. Chem. (2001) [Pubmed]
  23. A cytosolic protein-tyrosine phosphatase PTP1B specifically dephosphorylates and deactivates prolactin-activated STAT5a and STAT5b. Aoki, N., Matsuda, T. J. Biol. Chem. (2000) [Pubmed]
  24. Attenuation of leptin action and regulation of obesity by protein tyrosine phosphatase 1B. Cheng, A., Uetani, N., Simoncic, P.D., Chaubey, V.P., Lee-Loy, A., McGlade, C.J., Kennedy, B.P., Tremblay, M.L. Dev. Cell (2002) [Pubmed]
  25. Regulation of insulin-like growth factor type I (IGF-I) receptor kinase activity by protein tyrosine phosphatase 1B (PTP-1B) and enhanced IGF-I-mediated suppression of apoptosis and motility in PTP-1B-deficient fibroblasts. Buckley, D.A., Cheng, A., Kiely, P.A., Tremblay, M.L., O'Connor, R. Mol. Cell. Biol. (2002) [Pubmed]
  26. Purification of a murine protein-tyrosine/threonine kinase that phosphorylates and activates the Erk-1 gene product: relationship to the fission yeast byr1 gene product. Crews, C.M., Erikson, R.L. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  27. Protein-tyrosine phosphatase 1B expression is induced by inflammation in vivo. Zabolotny, J.M., Kim, Y.B., Welsh, L.A., Kershaw, E.E., Neel, B.G., Kahn, B.B. J. Biol. Chem. (2008) [Pubmed]
  28. Genetic ablation of protein tyrosine phosphatase 1B accelerates lymphomagenesis of p53-null mice through the regulation of B-cell development. Dubé, N., Bourdeau, A., Heinonen, K.M., Cheng, A., Loy, A.L., Tremblay, M.L. Cancer Res. (2005) [Pubmed]
  29. Reduction of protein tyrosine phosphatase 1B increases insulin-dependent signaling in ob/ob mice. Gum, R.J., Gaede, L.L., Koterski, S.L., Heindel, M., Clampit, J.E., Zinker, B.A., Trevillyan, J.M., Ulrich, R.G., Jirousek, M.R., Rondinone, C.M. Diabetes (2003) [Pubmed]
  30. Differential intracellular compartmentalization of phosphotyrosine phosphatases in a glial cell line: TC-PTP versus PTP-1B. Faure, R., Posner, B.I. Glia (1993) [Pubmed]
  31. Improvement of peripheral endothelial dysfunction by protein tyrosine phosphatase inhibitors in heart failure. Vercauteren, M., Remy, E., Devaux, C., Dautreaux, B., Henry, J.P., Bauer, F., Mulder, P., Hooft van Huijsduijnen, R., Bombrun, A., Thuillez, C., Richard, V. Circulation (2006) [Pubmed]
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