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Gene Review

PTPRA  -  protein tyrosine phosphatase, receptor...

Homo sapiens

Synonyms: HEPTP, HLPR, HPTPA, HPTPalpha, LRP, ...
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Disease relevance of PTPRA


Psychiatry related information on PTPRA


High impact information on PTPRA

  • Complementation and RNA-interference experiments showed that PTPA fulfills an essential function conserved from yeast to man [10].
  • PTPA binding to PP2A results in a dramatic alteration of substrate specificity, with enhanced phosphotyrosine phosphatase activity and decreased phosphoserine phosphatase activity [11].
  • To understand the molecular mechanism of PTPA activity, Ypa1 was cocrystallized with a proline-containing PPIase peptide substrate [12].
  • We conclude that Snx 17 binds to a motif in the LRP tail distinct from the endocytosis signals and promotes LRP sorting to the recycling pathway in the early endosomes [13].
  • The NPxY motif, proximal to the plasma membrane in the LRP cytoplasmic tail, is identified as the Snx 17-binding motif [13].

Chemical compound and disease context of PTPRA


Biological context of PTPRA

  • Phosphorylation of receptor protein-tyrosine phosphatase alpha on Tyr789, a binding site for the SH3-SH2-SH3 adaptor protein GRB-2 in vivo [18].
  • In this process, PTPalpha Ser-180 and Ser-204 phosphorylation is critical for the induction of phosphatase activity, which is required for dephosphorylation of pp60(c-src) [19].
  • The transmembrane and catalytic nature of PTPalpha indicate that it likely forms the transducing element of the complex, and we postulate that the role of contactin is to assemble a phosphorylation-competent system at the cell surface, conferring a dynamic signal transduction capability to the recognition element [20].
  • The HLPR genes is located on human chromosome 20, and the protein it encodes likely plays a fundamental role in the physiology of all cells as its expression appears to be ubiquitous [21].
  • Among transmembrane protein-tyrosine-phosphatases, the membrane distal catalytic domain (D2) of protein-tyrosine-phosphatase alpha (PTP alpha) is unusual in having low but detectable activity in the absence of the membrane proximal catalytic domain (D1) [22].

Anatomical context of PTPRA


Associations of PTPRA with chemical compounds

  • We show a physical interaction of PI 3-kinase and PKCdelta with PTPalpha and show that the tyrosine phosphatase plays a role in the activation of MAPK [19].
  • Taken together, we demonstrate the physical and functional association between PI 3-kinase, PKCdelta and PTPalpha in a signaling complex that mediates the antitumor activity of the somatostatin analogue TT-232 [19].
  • A phosphotyrosine displacement mechanism for activation of Src by PTPalpha [26].
  • We show that, dependent on serine hyperphosphorylation, protein tyrosine phosphatase alpha (PTPalpha) is activated by two different mechanisms during mitosis: its specific activity increases and its inhibitory binding to Grb2 decreases [27].
  • Receptor protein tyrosine phosphatase alpha participates in the m1 muscarinic acetylcholine receptor-dependent regulation of Kv1.2 channel activity [28].

Regulatory relationships of PTPRA


Other interactions of PTPRA

  • The cDNA clones thus isolated included LCA and six other novel receptor-like PTPases, named HPTP alpha, beta, gamma, delta, epsilon, and zeta [30].
  • Biochemical characterizations of these subclone cells showed that receptor-type protein-tyrosine phosphatase alpha (RPTPalpha) is elevated and ERK is constitutively activated, several folds higher than that in parental cells [2].
  • Overexpression of the wild type PTP alpha splice variant containing the 9 amino acids reduced insulin secretion, as did a mutant form unable to bind Grb2 (Tyr798Phe) [3].
  • In accordance with these results, LAR content was significantly increased, whereas LRP content was not increased [31].
  • As competitive inhibitors of PTP1B, ursolic acid and its derivative also inhibit T-cell protein tyrosine phosphatase and src homology phosphatase-2 but not leucocyte antigen-related phosphatase or protein tyrosine phosphatase alpha and epsilon, which are all possibly involved in the insulin pathway [32].

Analytical, diagnostic and therapeutic context of PTPRA


  1. Protein-tyrosine phosphatase alpha, RPTP alpha, is a Helicobacter pylori VacA receptor. Yahiro, K., Wada, A., Nakayama, M., Kimura, T., Ogushi, K., Niidome, T., Aoyagi, H., Yoshino, K., Yonezawa, K., Moss, J., Hirayama, T. J. Biol. Chem. (2003) [Pubmed]
  2. Receptor protein tyrosine phosphatase alpha signaling is involved in androgen depletion-induced neuroendocrine differentiation of androgen-sensitive LNCaP human prostate cancer cells. Zhang, X.Q., Kondrikov, D., Yuan, T.C., Lin, F.F., Hansen, J., Lin, M.F. Oncogene (2003) [Pubmed]
  3. The protein tyrosine phosphatase alpha modifies insulin secretion in INS-1E cells. Kapp, K., Metzinger, E., Kellerer, M., Häring, H.U., Lammers, R. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  4. Expression of protein tyrosine phosphatase alpha (RPTPalpha) in human breast cancer correlates with low tumor grade, and inhibits tumor cell growth in vitro and in vivo. Ardini, E., Agresti, R., Tagliabue, E., Greco, M., Aiello, P., Yang, L.T., Ménard, S., Sap, J. Oncogene (2000) [Pubmed]
  5. Extracellular signal-regulated kinase functions in the urokinase receptor-dependent pathway by which neutralization of low density lipoprotein receptor-related protein promotes fibrosarcoma cell migration and matrigel invasion. Webb, D.J., Nguyen, D.H., Gonias, S.L. J. Cell. Sci. (2000) [Pubmed]
  6. LRP in Alzheimer's disease: friend or foe? Ulery, P.G., Strickland, D.K. J. Clin. Invest. (2000) [Pubmed]
  7. Diverse patterns of expression of the 67-kD laminin receptor in human small intestinal mucosa: potential binding sites for prion proteins? Shmakov, A.N., Bode, J., Kilshaw, P.J., Ghosh, S. J. Pathol. (2000) [Pubmed]
  8. Amantadine influences cognitive processing in patients with multiple sclerosis. Sailer, M., Heinze, H.J., Schoenfeld, M.A., Hauser, U., Smid, H.G. Pharmacopsychiatry (2000) [Pubmed]
  9. Evidence of partial response activation in a memory-search task. Shin, E., Fabiani, M., Gratton, G. Brain research. Cognitive brain research. (2004) [Pubmed]
  10. A novel and essential mechanism determining specificity and activity of protein phosphatase 2A (PP2A) in vivo. Fellner, T., Lackner, D.H., Hombauer, H., Piribauer, P., Mudrak, I., Zaragoza, K., Juno, C., Ogris, E. Genes Dev. (2003) [Pubmed]
  11. Structure and mechanism of the phosphotyrosyl phosphatase activator. Chao, Y., Xing, Y., Chen, Y., Xu, Y., Lin, Z., Li, Z., Jeffrey, P.D., Stock, J.B., Shi, Y. Mol. Cell (2006) [Pubmed]
  12. Crystal structure of the PP2A phosphatase activator: implications for its PP2A-specific PPIase activity. Leulliot, N., Vicentini, G., Jordens, J., Quevillon-Cheruel, S., Schiltz, M., Barford, D., van Tilbeurgh, H., Goris, J. Mol. Cell (2006) [Pubmed]
  13. Sorting nexin 17 facilitates LRP recycling in the early endosome. van Kerkhof, P., Lee, J., McCormick, L., Tetrault, E., Lu, W., Schoenfish, M., Oorschot, V., Strous, G.J., Klumperman, J., Bu, G. EMBO J. (2005) [Pubmed]
  14. Insulin signaling and glucose homeostasis in mice lacking protein tyrosine phosphatase alpha. Le, H.T., Ponniah, S., Pallen, C.J. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  15. Adipocyte low density lipoprotein receptor-related protein gene expression and function is regulated by peroxisome proliferator-activated receptor gamma. Gauthier, A., Vassiliou, G., Benoist, F., McPherson, R. J. Biol. Chem. (2003) [Pubmed]
  16. A protective role of the low density lipoprotein receptor-related protein against amyloid beta-protein toxicity. Van Uden, E., Sagara, Y., Van Uden, J., Orlando, R., Mallory, M., Rockenstein, E., Masliah, E. J. Biol. Chem. (2000) [Pubmed]
  17. Platinum(IV) complex with adamantylamine overcomes intrinsic resistance to cisplatin in ovarian cancer cells. Horváth, V., Blanárová, O., Svihálková-Sindlerová, L., Soucek, K., Hofmanová, J., Sova, P., Kroutil, A., Fedorocko, P., Kozubík, A. Gynecol. Oncol. (2006) [Pubmed]
  18. Phosphorylation of receptor protein-tyrosine phosphatase alpha on Tyr789, a binding site for the SH3-SH2-SH3 adaptor protein GRB-2 in vivo. den Hertog, J., Tracy, S., Hunter, T. EMBO J. (1994) [Pubmed]
  19. Physical and functional interactions between protein tyrosine phosphatase alpha, PI 3-kinase, and PKCdelta. Steták, A., Csermely, P., Ullrich, A., Kéri, G. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  20. Protein tyrosine phosphatase alpha (PTPalpha) and contactin form a novel neuronal receptor complex linked to the intracellular tyrosine kinase fyn. Zeng, L., D'Alessandri, L., Kalousek, M.B., Vaughan, L., Pallen, C.J. J. Cell Biol. (1999) [Pubmed]
  21. Cloning and chromosomal assignment of a widely expressed human receptor-like protein-tyrosine phosphatase. Jirik, F.R., Janzen, N.M., Melhado, I.G., Harder, K.W. FEBS Lett. (1990) [Pubmed]
  22. Kinetic analysis of two closely related receptor-like protein-tyrosine-phosphatases, PTP alpha and PTP epsilon. Lim, K.L., Lai, D.S., Kalousek, M.B., Wang, Y., Pallen, C.J. Eur. J. Biochem. (1997) [Pubmed]
  23. Sequence of a cDNA encoding human LRP (leukocyte common antigen-related peptide). Ohagi, S., Nishi, M., Steiner, D.F. Nucleic Acids Res. (1990) [Pubmed]
  24. TNF-alpha and IFN-gamma down-regulate the expression of the metastasis-associated bi-functional 37LRP/p40 gene and protein in transformed keratinocytes. Clausse, N., van den Brûle, F., Delvenne, P., Jacobs, N., Franzen-Detrooz, E., Jackers, P., Castronovo, V. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  25. Lactoferrin promotes collagen gel contractile activity of fibroblasts mediated by lipoprotein receptors. Takayama, Y., Takezawa, T. Biochem. Cell Biol. (2006) [Pubmed]
  26. A phosphotyrosine displacement mechanism for activation of Src by PTPalpha. Zheng, X.M., Resnick, R.J., Shalloway, D. EMBO J. (2000) [Pubmed]
  27. Two mechanisms activate PTPalpha during mitosis. Zheng, X.M., Shalloway, D. EMBO J. (2001) [Pubmed]
  28. Receptor protein tyrosine phosphatase alpha participates in the m1 muscarinic acetylcholine receptor-dependent regulation of Kv1.2 channel activity. Tsai, W., Morielli, A.D., Cachero, T.G., Peralta, E.G. EMBO J. (1999) [Pubmed]
  29. Receptor-like protein-tyrosine phosphatase alpha specifically inhibits insulin-increased prolactin gene expression. Jacob, K.K., Sap, J., Stanley, F.M. J. Biol. Chem. (1998) [Pubmed]
  30. Structural diversity and evolution of human receptor-like protein tyrosine phosphatases. Krueger, N.X., Streuli, M., Saito, H. EMBO J. (1990) [Pubmed]
  31. High glucose-induced abnormal epidermal growth factor signaling. Obata, T., Maegawa, H., Kashiwagi, A., Pillay, T.S., Kikkawa, R. J. Biochem. (1998) [Pubmed]
  32. Ursolic acid and its derivative inhibit protein tyrosine phosphatase 1B, enhancing insulin receptor phosphorylation and stimulating glucose uptake. Zhang, W., Hong, D., Zhou, Y., Zhang, Y., Shen, Q., Li, J.Y., Hu, L.H., Li, J. Biochim. Biophys. Acta (2006) [Pubmed]
  33. The gene for receptor-linked protein-tyrosine-phosphatase (PTPA) is assigned to human chromosome 20p12-pter by in situ hybridization (ISH and FISH). Rao, V.V., Löffler, C., Sap, J., Schlessinger, J., Hansmann, I. Genomics (1992) [Pubmed]
  34. Calmodulin binds to and inhibits the activity of the membrane distal catalytic domain of receptor protein-tyrosine phosphatase alpha. Liang, L., Lim, K.L., Seow, K.T., Ng, C.H., Pallen, C.J. J. Biol. Chem. (2000) [Pubmed]
  35. Decreased expression of both the low-density lipoprotein receptor-related protein/alpha(2)-macroglobulin receptor and its receptor-associated protein in late stages of cutaneous melanocytic tumor progression. de Vries, T.J., Verheijen, J.H., de Bart, A.C., Weidle, U.H., Ruiter, D.J., van Muijen, G.N. Cancer Res. (1996) [Pubmed]
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