Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

PTPe (RPTPe and Cyt-PTPe)

  • Ari ElsonEmail author
  • Liat Rousso-Noori
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_525


Historical Background

Phosphorylation of tyrosine residues in proteins is one of the better-studied molecular mechanisms for regulating protein structure and function and with it – the function of cells and organisms. Tyrosine phosphorylation is a reversible process that is controlled by the opposing activities of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). The numbers of PTKs and PTPs are similar and small relative to the numbers of their potential substrates; there are 81 and 85 genes that yield active, protein-specific PTPs and PTKs, respectively (Alonso et al. 2004). As a result, individual PTPs and PTKs each target multiple substrates and fulfill distinct roles in different physiological systems. Although PTPs were first described in molecular terms in 1988, about a decade after PTKs, both protein superfamilies are now recognized as critical regulators of protein...

This is a preview of subscription content, log in to check access.


  1. Aga-Mizrachi S, Brutman-Barazani T, Jacob AI, Bak A, Elson A, Sampson SR. Cytosolic protein tyrosine phosphatase-epsilon is a negative regulator of insulin signaling in skeletal muscle. Endocrinology. 2008;149(2):605–14.CrossRefPubMedGoogle Scholar
  2. Akimoto M, Mishra K, Lim KT, Tani N, Hisanaga SI, Katagiri T, et al. Protein tyrosine phosphatase epsilon is a negative regulator of FcepsilonRI-mediated mast cell responses. Scand J Immunol. 2009;69(5):401–11.CrossRefPubMedGoogle Scholar
  3. Alonso A, Sasin J, Bottini N, Friedberg I, Osterman A, Godzik A, et al. Protein tyrosine phosphatases in the human genome. Cell. 2004;117(6):699–711.CrossRefPubMedGoogle Scholar
  4. Andersen JN, Elson A, Lammers R, Romer J, Clausen JT, Moller KB, et al. Comparative study of protein tyrosine phosphatase-epsilon isoforms: membrane localization confers specificity in cellular signalling. Biochem J. 2001a;354(Pt 3):581–90.PubMedPubMedCentralGoogle Scholar
  5. Andersen JN, Mortensen OH, Peters GH, Drake PG, Iversen LF, Olsen OH, et al. Structural and evolutionary relationships among protein tyrosine phosphatase domains. Mol Cell Biol. 2001b;21(21):7117–36.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Berman-Golan D, Elson A. Neu-mediated phosphorylation of protein tyrosine phosphatase epsilon is critical for activation of Src in mammary tumor cells. Oncogene. 2007;26(49):7028–37.CrossRefPubMedGoogle Scholar
  7. De Franceschi L, Biondani A, Carta F, Turrini F, Laudanna C, Deana R, et al. PTPepsilon has a critical role in signaling transduction pathways and phosphoprotein network topology in red cells. Proteomics. 2008;8(22):4695–708.PubMedPubMedCentralCrossRefGoogle Scholar
  8. den Hertog J, Ostman A, Bohmer FD. Protein tyrosine phosphatases: regulatory mechanisms. FEBS J. 2008;275(5):831–47.CrossRefGoogle Scholar
  9. Elson A. Protein tyrosine phosphatase epsilon increases the risk of mammary hyperplasia and mammary tumors in transgenic mice. Oncogene. 1999;18(52):7535–42.CrossRefPubMedGoogle Scholar
  10. Elson A, Leder P. Identification of a cytoplasmic, phorbol ester-inducible isoform of protein tyrosine phosphatase epsilon. Proc Natl Acad Sci USA. 1995a;92(26):12235–9.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Elson A, Leder P. Protein-tyrosine phosphatase epsilon. An isoform specifically expressed in mouse mammary tumors initiated by v-Ha-ras OR neu. J Biol Chem. 1995b;270(44):26116–22.CrossRefPubMedGoogle Scholar
  12. Gil-Henn H, Elson A. Tyrosine phosphatase-epsilon activates Src and supports the transformed phenotype of Neu-induced mammary tumor cells. J Biol Chem. 2003;278(18):15579–86.CrossRefPubMedGoogle Scholar
  13. Gil-Henn H, Volohonsky G, Toledano-Katchalski H, Gandre S, Elson A. Generation of novel cytoplasmic forms of protein tyrosine phosphatase epsilon by proteolytic processing and translational control. Oncogene. 2000;19(38):4375–84.CrossRefPubMedGoogle Scholar
  14. Gil-Henn H, Volohonsky G, Elson A. Regulation of protein-tyrosine phosphatases alpha and epsilon by calpain-mediated proteolytic cleavage. J Biol Chem. 2001;276(34):31772–9.CrossRefPubMedGoogle Scholar
  15. Granot-Attas S, Luxenburg C, Finkelshtein E, Elson A. PTP epsilon regulates integrin-mediated podosome stability in osteoclasts by activating src. Mol Biol Cell. 2009;20(20):4324–34.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Hendriks WJ, Elson A, Harroch S, Stoker AW. Protein tyrosine phosphatases: functional inferences from mouse models and human diseases. FEBS J. 2008;275(5):816–30.CrossRefPubMedGoogle Scholar
  17. Krueger NX, Streuli M, Saito H. Structural diversity and evolution of human receptor-like protein tyrosine phosphatases. EMBO J. 1990;9:3241–52.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Muja N, Lovas G, Romm E, Machleder D, Ranjan M, Gallo V, et al. Expression of a catalytically inactive transmembrane protein tyrosine phosphatase epsilon (tm-PTP epsilon) delays optic nerve myelination. Glia. 2004;48(4):278–97.CrossRefPubMedGoogle Scholar
  19. Nakagawa Y, Yamada N, Shimizu H, Shiota M, Tamura M, Kim-Mitsuyama S, et al. Tyrosine phosphatase epsilonM stimulates migration and survival of porcine aortic endothelial cells by activating c-Src. Biochem Biophys Res Commun. 2004;325(1):314–9.CrossRefPubMedGoogle Scholar
  20. Nakagawa Y, Aoki N, Aoyama K, Shimizu H, Shimano H, Yamada N, et al. Receptor-type protein tyrosine phosphatase epsilon (PTPepsilonM) is a negative regulator of insulin signaling in primary hepatocytes and liver. Zool Sci. 2005;22(2):169–75.CrossRefPubMedGoogle Scholar
  21. Nakamura K, Mizuno Y, Kikuchi K. Molecular cloning of a novel cytoplasmic protein tyrosine phosphatase PTP epsilon. Biochem Biophys Res Commun. 1996;218:726–32.CrossRefPubMedGoogle Scholar
  22. Peretz A, Gil-Henn H, Sobko A, Shinder V, Attali B, Elson A. Hypomyelination and increased activity of voltage-gated K(+) channels in mice lacking protein tyrosine phosphatase epsilon. EMBO J. 2000;19:4036–45.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Rousso-Noori L, Knobler H, Levy-Apter E, Kuperman Y, Neufeld-Cohen A, Keshet Y, et al. Protein tyrosine phosphatase epsilon affects body weight by downregulating leptin signaling in a phosphorylation-dependent manner. Cell Metab. 2011;13(5):562–72.CrossRefPubMedGoogle Scholar
  24. Sines T, Granot-Attas S, Weisman-Welcher S, Elson A. Association of tyrosine phosphatase epsilon with microtubules inhibits phosphatase activity and is regulated by the epidermal growth factor receptor. Mol Cell Biol. 2007;27(20):7102–12.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Sully V, Pownall S, Vincan E, Bassal S, Borowski AH, Hart PH, et al. Functional abnormalities in protein tyrosine phosphatase epsilon-deficient macrophages. Biochem Biophys Res Commun. 2001;286:184–8.CrossRefPubMedGoogle Scholar
  26. Tanuma N, Nakamura K, Kikuchi K. Distinct promoters control transmembrane and cytosolic protein tyrosine phosphatase epsilon expression during macrophage differentiation. Eur J Biochem. 1999;259:46–54.CrossRefPubMedGoogle Scholar
  27. Tanuma N, Shima H, Nakamura K, Kikuchi K. Protein tyrosine phosphatase epsilonC selectively inhibits interleukin-6- and interleukin- 10-induced JAK-STAT signaling. Blood. 2001;98:3030–4.CrossRefPubMedGoogle Scholar
  28. Tanuma N, Shima H, Shimada S, Kikuchi K. Reduced tumorigenicity of murine leukemia cells expressing protein-tyrosine phosphatase, PTPepsilon C. Oncogene. 2003;22(12):1758–62.CrossRefPubMedGoogle Scholar
  29. Thompson LJ, Jiang J, Madamanchi N, Runge MS, Patterson C. PTP-epsilon, a tyrosine phosphatase expressed in endothelium, negatively regulates endothelial cell proliferation. Am J Physiol Heart Circ Physiol. 2001;281:H396–403.CrossRefPubMedGoogle Scholar
  30. Toledano-Katchalski H, Tiran Z, Sines T, Shani G, Granot-Attas S, den Hertog J, et al. Dimerization in vivo and inhibition of the nonreceptor form of protein tyrosine phosphatase epsilon. Mol Cell Biol. 2003;23(15):5460–71.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Tonks NK. Protein tyrosine phosphatases: from genes, to function, to disease. Nat Rev Mol Cell Biol. 2006;7(11):833–46.CrossRefPubMedGoogle Scholar
  32. Wabakken T, Hauge H, Funderud S, Aasheim HC. Characterization, expression and functional aspects of a novel protein tyrosine phosphatase epsilon isoform. Scand J Immunol. 2002;56(3):276–85.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Molecular Genetics, Arnold R. Meyer Institute of Biological SciencesThe Weizmann Institute of ScienceRehovotIsrael