Gene Symbol: Ptpn1
Description: protein tyrosine phosphatase, non-receptor type 1
Alias: Ptp, tyrosine-protein phosphatase non-receptor type 1, PTP-1B, protein-tyrosine phosphatase 1B
Species: rat
Products:     Ptpn1

Top Publications

  1. Guan K, Haun R, Watson S, Geahlen R, Dixon J. Cloning and expression of a protein-tyrosine-phosphatase. Proc Natl Acad Sci U S A. 1990;87:1501-5 pubmed
    ..Sequences located at the C terminus of the rat brain PTPase contain possible sites for phosphorylation as well as signals which could serve for membrane attachment. ..
  2. Chang Y, Ceacareanu B, Zhuang D, Zhang C, Pu Q, Ceacareanu A, et al. Counter-regulatory function of protein tyrosine phosphatase 1B in platelet-derived growth factor- or fibroblast growth factor-induced motility and proliferation of cultured smooth muscle cells and in neointima formation. Arterioscler Thromb Vasc Biol. 2006;26:501-7 pubmed
    ..factor-BB (PDGF-BB) or fibroblast growth factor-2 (FGF2) increases the levels of protein tyrosine phosphatase (PTP)1B...
  3. Milarski K, Zhu G, Pearl C, McNamara D, Dobrusin E, MacLean D, et al. Sequence specificity in recognition of the epidermal growth factor receptor by protein tyrosine phosphatase 1B. J Biol Chem. 1993;268:23634-9 pubmed
    ..The results revealed clear sequence specificity in the binding of proteins involved in the regulation of intracellular signaling by receptor tyrosine kinases. ..
  4. Frangioni J, Beahm P, Shifrin V, Jost C, Neel B. The nontransmembrane tyrosine phosphatase PTP-1B localizes to the endoplasmic reticulum via its 35 amino acid C-terminal sequence. Cell. 1992;68:545-60 pubmed
    We report the first intracellular characterization of an endogenous nontransmembrane protein tyrosine phosphatase (PTP)...
  5. Matozo H, Nascimento A, Santos M, Iuliano R, Fusco A, Polikarpov I. Crystallization and preliminary X-ray diffraction analysis of rat protein tyrosine phosphatase eta. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006;62:923-5 pubmed
    ..Diffraction data were collected to 1.87 A resolution. The crystal belongs to space group P2(1)2(1)2(1), with unit-cell parameters a = 46.46, b = 63.07, c = 111.64 A, and contains one molecule per asymmetric unit. ..
  6. Krishnan N, Fu C, Pappin D, Tonks N. H2S-Induced sulfhydration of the phosphatase PTP1B and its role in the endoplasmic reticulum stress response. Sci Signal. 2011;4:ra86 pubmed publisher
    ..Together, these data define a signaling function for H(2)S in inhibiting PTP1B activity and thereby promoting PERK activity during the response to ER stress. ..
  7. Ito Y, Banno R, Hagimoto S, Ozawa Y, Arima H, Oiso Y. TNF? increases hypothalamic PTP1B activity via the NF?B pathway in rat hypothalamic organotypic cultures. Regul Pept. 2012;174:58-64 pubmed publisher
    ..The expression levels of hypothalamic protein tyrosine phosphatase 1B (PTP1B), a negative regulator of leptin and insulin signaling, are also elevated by HFD, and several ..
  8. Hébert Chatelain E, Dupuy J, Letellier T, Dachary Prigent J. Functional impact of PTP1B-mediated Src regulation on oxidative phosphorylation in rat brain mitochondria. Cell Mol Life Sci. 2011;68:2603-13 pubmed publisher
    ..Our analysis emphasizes the regulatory function of Src and its modulation by PTP1B on oxidative phosphorylation in mitochondria. ..
  9. Zabolotny J, Kim Y, Welsh L, Kershaw E, Neel B, Kahn B. Protein-tyrosine phosphatase 1B expression is induced by inflammation in vivo. J Biol Chem. 2008;283:14230-41 pubmed publisher
    ..Our data suggest that PTP1B overexpression in multiple tissues in obesity is regulated by inflammation and that PTP1B may be a target of anti-inflammatory therapies. ..

More Information


  1. Fuentes F, Zimmer D, Atienza M, Schottenfeld J, Penkala I, BALE T, et al. Protein tyrosine phosphatase PTP1B is involved in hippocampal synapse formation and learning. PLoS ONE. 2012;7:e41536 pubmed publisher
    ..Disruption of hippocampal PTP1B function or expression leads to elongation of dendritic filopodia and improved learning and memory, demonstrating an exciting novel role for this phosphatase. ..
  2. Yan W, Pan C, Dou J, Ma F, Wang X, Yang G, et al. [Effects of candesartan on expressions of JAK2 and PTP-1B in adipose tissue of high-fat diet-fed rats]. Zhonghua Yi Xue Za Zhi. 2010;90:1836-40 pubmed
    To observe the effects of candesartan on the expressions of JAK2 and protein tyrosine phosphatase-1B (PTP-1B) in adipose tissue of obese rats induced by high-fat diet...
  3. Ahmad F, Goldstein B. Purification, identification and subcellular distribution of three predominant protein-tyrosine phosphatase enzymes in skeletal muscle tissue. Biochim Biophys Acta. 1995;1248:57-69 pubmed
    ..These studies provide insight into the relative abundance and subcellular distribution of specific PTPases in muscle tissue that are involved in the regulation of reversible tyrosine phosphorylation in this tissue. ..
  4. Sangwan V, Paliouras G, Abella J, Dubé N, Monast A, Tremblay M, et al. Regulation of the Met receptor-tyrosine kinase by the protein-tyrosine phosphatase 1B and T-cell phosphatase. J Biol Chem. 2008;283:34374-83 pubmed publisher
    ..Our data demonstrate that PTP1B and TCPTP play distinct and non-redundant roles in the regulation of the Met receptor-tyrosine kinase. ..
  5. Liu F, Hill D, Chernoff J. Direct binding of the proline-rich region of protein tyrosine phosphatase 1B to the Src homology 3 domain of p130(Cas). J Biol Chem. 1996;271:31290-5 pubmed
    b>Protein tyrosine phosphatase 1B (PTP1B) is an abundant intracellular enzyme that is thought to act as a negative regulator of certain signaling pathways...
  6. Bettaieb A, Liu S, Xi Y, Nagata N, Matsuo K, Matsuo I, et al. Differential regulation of endoplasmic reticulum stress by protein tyrosine phosphatase 1B and T cell protein tyrosine phosphatase. J Biol Chem. 2011;286:9225-35 pubmed publisher
  7. Galic S, Hauser C, Kahn B, Haj F, Neel B, Tonks N, et al. Coordinated regulation of insulin signaling by the protein tyrosine phosphatases PTP1B and TCPTP. Mol Cell Biol. 2005;25:819-29 pubmed
    ..These results demonstrate that PTP1B and TCPTP are not redundant in insulin signaling and that they act to control both common as well as distinct insulin signaling pathways in the same cell. ..
  8. Arachiche A, Augereau O, Decossas M, Pertuiset C, Gontier E, Letellier T, et al. Localization of PTP-1B, SHP-2, and Src exclusively in rat brain mitochondria and functional consequences. J Biol Chem. 2008;283:24406-11 pubmed publisher
    An immunodetection study of protein tyrosine phosphatase 1B (PTP-1B), SHP-2, and Src in isolated mitochondria from different rat tissues (brain, muscle, heart, liver, and kidney) revealed their exclusive localization in the brain...
  9. Zhuang D, Pu Q, Ceacareanu B, Chang Y, Dixit M, Hassid A. Chronic insulin treatment amplifies PDGF-induced motility in differentiated aortic smooth muscle cells by suppressing the expression and function of PTP1B. Am J Physiol Heart Circ Physiol. 2008;295:H163-73 pubmed publisher
    ..These observations uncover novel mechanisms that explain how insulin amplifies the motogenic capacity of the pivotal growth factor PDGF. ..
  10. Lanahan A, Zhang X, Fantin A, Zhuang Z, Rivera Molina F, Speichinger K, et al. The neuropilin 1 cytoplasmic domain is required for VEGF-A-dependent arteriogenesis. Dev Cell. 2013;25:156-68 pubmed publisher
    ..This led to increased PTPN1 (PTP1b)-mediated dephosphorylation of VEGFR2 at Y(1175), the site involved in activating ERK signaling...
  11. Bettaieb A, Koike S, Chahed S, Bachaalany S, Griffey S, Sastre J, et al. Pancreatic Protein Tyrosine Phosphatase 1B Deficiency Exacerbates Acute Pancreatitis in Mice. Am J Pathol. 2016;186:2043-2054 pubmed publisher
    ..b>Protein tyrosine phosphatase 1B (PTP1B) is implicated in inflammatory signaling, but its significance in AP remains unclear...
  12. Lu B, Gu P, Xu Y, Ye X, Wang Y, Du H, et al. Overexpression of protein tyrosine phosphatase 1B impairs glucose-stimulated insulin secretion in INS-1 cells. Minerva Endocrinol. 2016;41:1-9 pubmed
    b>Protein tyrosine phosphatase 1B (PTP1B) has been implicated as a negative regulator of insulin signaling...
  13. Zhen X, Torres C, Cai G, Friedman E. Inhibition of protein tyrosine/mitogen-activated protein kinase phosphatase activity is associated with D2 dopamine receptor supersensitivity in a rat model of Parkinson's disease. Mol Pharmacol. 2002;62:1356-63 pubmed
    ..Stimulation of D(2)DR induced a 60% inhibition in protein tyrosine phosphatase (PTP) activity but not in PSP activity in lesioned striata...
  14. Zhang Z, Thieme Sefler A, MacLean D, McNamara D, Dobrusin E, Sawyer T, et al. Substrate specificity of the protein tyrosine phosphatases. Proc Natl Acad Sci U S A. 1993;90:4446-50 pubmed
    ..The results demonstrate that chemical features in the primary structure surrounding the dephosphorylation site contribute to PTPase substrate specificity. ..
  15. Morrison C, White C, Wang Z, Lee S, Lawrence D, Cefalu W, et al. Increased hypothalamic protein tyrosine phosphatase 1B contributes to leptin resistance with age. Endocrinology. 2007;148:433-40 pubmed
    ..To identify potential cellular mediators of this resistance, we focused on protein tyrosine phosphatase 1B (PTP1B), a recently described inhibitor of leptin signaling...
  16. Hashimoto N, Zhang W, Goldstein B. Insulin receptor and epidermal growth factor receptor dephosphorylation by three major rat liver protein-tyrosine phosphatases expressed in a recombinant bacterial system. Biochem J. 1992;284 ( Pt 2):569-76 pubmed
  17. Ropelle E, Pauli J, Prada P, De Souza C, Picardi P, Faria M, et al. Reversal of diet-induced insulin resistance with a single bout of exercise in the rat: the role of PTP1B and IRS-1 serine phosphorylation. J Physiol. 2006;577:997-1007 pubmed
    ..Diet-induced obesity (DIO) increased the expression and activity of the protein tyrosine phosphatase 1B (PTP1B) and attenuated insulin signalling in gastrocnemius muscle of rats, a phenomenon which was ..
  18. Shimizu S, Ugi S, Maegawa H, Egawa K, Nishio Y, Yoshizaki T, et al. Protein-tyrosine phosphatase 1B as new activator for hepatic lipogenesis via sterol regulatory element-binding protein-1 gene expression. J Biol Chem. 2003;278:43095-101 pubmed
    ..We demonstrate here a unique serial activation of the PTP1B-PP2A axis as a novel mechanism for the regulation of gene expression in the biosynthesis of triglyceride. ..
  19. Nievergall E, Janes P, Stegmayer C, Vail M, Haj F, Teng S, et al. PTP1B regulates Eph receptor function and trafficking. J Cell Biol. 2010;191:1189-203 pubmed publisher
    ..Our studies for the first time provide molecular, mechanistic, and functional insights into the role of PTP1B controlling Eph/ephrin-facilitated cellular interactions. ..
  20. Di Paola R, Frittitta L, Miscio G, Bozzali M, Baratta R, Centra M, et al. A variation in 3' UTR of hPTP1B increases specific gene expression and associates with insulin resistance. Am J Hum Genet. 2002;70:806-12 pubmed
    b>Protein tyrosine phosphatase 1B (PTP1B) inhibits insulin signaling and, when overexpressed, plays a role in insulin resistance (Ahmad et al. 1997)...
  21. Shi K, Ugi S, Shimizu S, Sekine O, Ikeda K, Egawa K, et al. Membrane localization of protein-tyrosine phosphatase 1B is essential for its activation of sterol regulatory element-binding protein-1 gene expression. Biochem Biophys Res Commun. 2007;363:626-32 pubmed
    ..In conclusion, membrane localization of PTP1B is essential for PP2A activation, which is crucial for its enhancement of SREBP-1 gene expression. ..
  22. Lyu J, Zheng G, Chen Z, Wang B, Tao S, Xiang D, et al. Sepsis-induced brain mitochondrial dysfunction is associated with altered mitochondrial Src and PTP1B levels. Brain Res. 2015;1620:130-8 pubmed publisher
    ..In this study, we investigated the roles of the tyrosine kinase Src and protein tyrosine phosphatase 1B (PTP1B) in brain mitochondrial dysfunction using a rat model of lipopolysaccharide (LPS)-induced ..
  23. Gu F, Nguyen D, Stuible M, Dubé N, Tremblay M, Chevet E. Protein-tyrosine phosphatase 1B potentiates IRE1 signaling during endoplasmic reticulum stress. J Biol Chem. 2004;279:49689-93 pubmed
    Protein-tyrosine phosphatase 1B (PTP-1B) is the prototypic tyrosine phosphatase whose function in insulin signaling and metabolism is well established...
  24. Dadke S, Chernoff J. Protein-tyrosine phosphatase 1B mediates the effects of insulin on the actin cytoskeleton in immortalized fibroblasts. J Biol Chem. 2003;278:40607-11 pubmed
    ..These results show that PTP1B, best known as a negative regulator of the metabolic effects of insulin, is required for the effects of insulin on actin organization in immortalized fibroblasts. ..
  25. Ponnusamy M, Ma L, Zhuang S. Necrotic renal epithelial cell inhibits renal interstitial fibroblast activation: role of protein tyrosine phosphatase 1B. Am J Physiol Renal Physiol. 2013;304:F698-709 pubmed publisher
    ..The presence of sodium orthovanadate, a general protein tyrosine phosphatase (PTP) inhibitor or TCS-401 (a selective PTP1B inhibitor), abrogated those effects of RPTC-Sup, whereas coincubation with ..
  26. Lund I, Hansen J, Andersen H, Møller N, Billestrup N. Mechanism of protein tyrosine phosphatase 1B-mediated inhibition of leptin signalling. J Mol Endocrinol. 2005;34:339-51 pubmed
    ..In conclusion, these results suggested that the negative regulatory role of PTP1B on leptin signalling is mediated through a direct and selective dephosphorylation of the two signalling molecules, JAK2 and STAT3. ..
  27. 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
  28. Valentino L, Pierre J. JAK/STAT signal transduction: regulators and implication in hematological malignancies. Biochem Pharmacol. 2006;71:713-21 pubmed
    ..Among them phosphotyrosine phosphatases (SHPs, CD45, PTP1B/TC-PTP), protein inhibitors of activated STATs (PIAS) and suppressors of cytokine signaling (SOCS) inhibit specific and ..
  29. Zhuang D, Balani P, Pu Q, Thakran S, Hassid A. Suppression of PKG by PDGF or nitric oxide in differentiated aortic smooth muscle cells: obligatory role of protein tyrosine phosphatase 1B. Am J Physiol Heart Circ Physiol. 2011;300:H57-63 pubmed publisher
    Treatment of aortic smooth muscle cells with PDGF induces the upregulation of protein tyrosine phosphatase 1B (PTP1B). PTP1B, in turn, decreases the function of several growth factor receptors, thus completing a negative feedback loop...
  30. Hirata A, Alvarez Rojas F, Carvalheira J, Carvalho C, Dolnikoff M, Abdalla Saad M. Modulation of IR/PTP1B interaction and downstream signaling in insulin sensitive tissues of MSG-rats. Life Sci. 2003;73:1369-81 pubmed
    ..In 28-week-old-MSG rats there was an increase in IR/PTP1B interaction and reduced insulin signaling in liver, muscle and adipocytes, and a more pronounced insulin resistance. ..
  31. Mendes N, Castro G, Guadagnini D, Tobar N, Cognuck S, Elias L, et al. Knocking down amygdalar PTP1B in diet-induced obese rats improves insulin signaling/action, decreases adiposity and may alter anxiety behavior. Metabolism. 2017;70:1-11 pubmed publisher
    b>Protein tyrosine phosphatase 1B (PTP1B) has been extensively implicated in the regulation of body weight, food intake, and energy expenditure. The role of PTP1B appears to be cell and brain region dependent...
  32. Arnold A, Nautiyal M, Diz D. Protein phosphatase 1b in the solitary tract nucleus is necessary for normal baroreflex function. J Cardiovasc Pharmacol. 2012;59:472-8 pubmed publisher
    ..These results suggest that PTP1b within the NTS may be a novel molecular mechanism for preservation of resting baroreflex function and provides further evidence for deleterious cardiovascular effects associated with PTP1b inhibition. ..
  33. Zhong S, Xu J, Li P, Tsukamoto H. Caveosomal oxidative stress causes Src-p21ras activation and lysine 63 TRAF6 protein polyubiquitination in iron-induced M1 hepatic macrophage activation. J Biol Chem. 2012;287:32078-84 pubmed publisher
    ..that Fe(2+) induces generation of superoxide anion (O(2)()) in endosomes, reduces protein-tyrosine phosphatase (PTP) activity, and activates Src at 2?10 min of Fe(2+) addition to rat primary HM culture...
  34. DU Z, Hu L, Zhao G, Li Y, Ma Z. Protein tyrosine phosphatase 1B regulates the activity of retinal pigment epithelial cells. Mol Vis. 2015;21:523-31 pubmed
    To determine whether protein tyrosine phosphatase 1B (PTP1B) is expressed in rat retinal pigment epithelium (RPE) cells, to evaluate whether inhibition of PTP1B contributes to initiation of RPE cells into an active state, and to ..
  35. Persson C, Sävenhed C, Bourdeau A, Tremblay M, Markova B, Bohmer F, et al. Site-selective regulation of platelet-derived growth factor beta receptor tyrosine phosphorylation by T-cell protein tyrosine phosphatase. Mol Cell Biol. 2004;24:2190-201 pubmed
    ..To explore whether T-cell PTP (TC-PTP) negatively regulates the PDGF beta receptor, we compared PDGF beta receptor tyrosine phosphorylation in ..
  36. Nezvitsky L, Tremblay M, Takano T, Papillon J, Cybulsky A. Complement-mediated glomerular injury is reduced by inhibition of protein-tyrosine phosphatase 1B. Am J Physiol Renal Physiol. 2014;307:F634-47 pubmed publisher
    ..The cytoprotective effects of PTP1B deletion in cultured cells and in anti-glomerular basement membrane nephritis suggest that PTP1B may potentially be a therapeutic target in complement-mediated diseases. ..
  37. Barbieri F, Pattarozzi A, Gatti M, Porcile C, Bajetto A, Ferrari A, et al. Somatostatin receptors 1, 2, and 5 cooperate in the somatostatin inhibition of C6 glioma cell proliferation in vitro via a phosphotyrosine phosphatase-eta-dependent inhibition of extracellularly regulated kinase-1/2. Endocrinology. 2008;149:4736-46 pubmed publisher
    ..The combined activation of SSTR1 and -2 shows a partial synergism as far as antiproliferative activity, whereas SSTR2 and -5 activation results in a response resembling the SSTR5 effects. ..
  38. Zhu X, Zhou Y, Tao R, Zhao J, Chen J, Liu C, et al. Upregulation of PTP1B After Rat Spinal Cord Injury. Inflammation. 2015;38:1891-902 pubmed publisher
    b>Protein tyrosine phosphatase 1B (PTP1B), a member of the protein tyrosine phosphatase family, attaches to the endoplasmic reticulum (ER) via its C-terminal tail...
  39. Tsuchiya A, Nagaya H, Kanno T, Nishizaki T. Oleic acid stimulates glucose uptake into adipocytes by enhancing insulin receptor signaling. J Pharmacol Sci. 2014;126:337-43 pubmed publisher
    ..In the cell-free assay of protein tyrosine phosphatase 1B (PTP1B), cis-unsaturated FFAs such as linoleic, linolenic, and oleic acid significantly suppressed ..
  40. Zhang Z, Walsh A, Wu L, McNamara D, Dobrusin E, Miller W. Determinants of substrate recognition in the protein-tyrosine phosphatase, PTP1. J Biol Chem. 1996;271:5386-92 pubmed
    ..The results are discussed in light of the crystal structure of human PTP1B and suggest that an additional mode of substrate recognition must exist for PTP1 catalysis. ..
  41. Ugi S, Shi K, Nishio Y, Shimizu S, Guo B, Sekine O, et al. Membrane localization of protein-tyrosine phosphatase 1B is essential for its activation of sterol regulatory element-binding protein-1 gene expression and consequent hypertriglyceridaemia. J Biochem. 2009;146:541-7 pubmed publisher
    ..Our results indicate that activation of PTP1B in the liver could induce hypertriglyceridaemia and that anchoring of PTP1B to the membrane is crucial for its action. ..
  42. Harris D, Joyce N. Protein tyrosine phosphatase, PTP1B, expression and activity in rat corneal endothelial cells. Mol Vis. 2007;13:785-96 pubmed
  43. Krezel A, Maret W. Thionein/metallothionein control Zn(II) availability and the activity of enzymes. J Biol Inorg Chem. 2008;13:401-9 pubmed
    ..b>Protein tyrosine phosphatase 1B (PTP 1B), on the other hand, is not classified as a zinc enzyme but is strongly inhibited by Zn(II), ..
  44. Lee J, Yoo S, Kim J, Lee J, Kim B, Park K, et al. Early life stress experience may blunt hypothalamic leptin signalling. J Biosci. 2017;42:131-138 pubmed
    ..The results suggest that neonatal MS experience may blunt the anorectic efficacy of leptin later in life, possibly in relation with increased expressions of PTP1B and/or pSTAT3 in the hypothalamus. ..
  45. Borges B, Rorato R, Uchoa E, Marangon P, Elias C, Antunes Rodrigues J, et al. Protein tyrosine phosphatase-1B contributes to LPS-induced leptin resistance in male rats. Am J Physiol Endocrinol Metab. 2015;308:E40-50 pubmed publisher
    ..Our findings contribute to understanding the mechanisms involved in leptin resistance during low-grade inflammation as seen in obesity. ..
  46. Youngren J. Regulation of insulin receptor function. Cell Mol Life Sci. 2007;64:873-91 pubmed
    ..The impact of these processes on the conformational changes and phosphorylation events required for full signaling activity, as well as the role of these mechanisms in human disease, is reviewed in this article. ..
  47. Sangwan V, Abella J, Lai A, Bertos N, Stuible M, Tremblay M, et al. Protein-tyrosine phosphatase 1B modulates early endosome fusion and trafficking of Met and epidermal growth factor receptors. J Biol Chem. 2011;286:45000-13 pubmed publisher
    ..Finally, we show that PTP1B dephosphorylated NSF and that this interaction was required for physiological RTK trafficking and appropriate attenuation of downstream signaling. ..
  48. Obanda D, Cefalu W. Modulation of cellular insulin signaling and PTP1B effects by lipid metabolites in skeletal muscle cells. J Nutr Biochem. 2013;24:1529-37 pubmed publisher
    ..tissue - may attenuate insulin signaling through the protein kinase B (AKt) pathway and up-regulate protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin signaling...
  49. Chang Y, Zhuang D, Zhang C, Hassid A. Increase of PTP levels in vascular injury and in cultured aortic smooth muscle cells treated with specific growth factors. Am J Physiol Heart Circ Physiol. 2004;287:H2201-8 pubmed indicated that vascular injury is associated with increased mRNA levels of protein tyrosine phosphatase (PTP)-1B (PTP-1B)...