The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

PTPRU  -  protein tyrosine phosphatase, receptor...

Homo sapiens

Synonyms: FMI, PCP-2, PCP2, PTP, PTP pi, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of PTPRU

  • The identification of specific binding partners for this receptor-like PTP provides insight into the mechanisms of its biological action and suggests a role for hPTPkappa in the regulation of processes involving cell contact and adhesion such as growth control, tumor invasion, and metastasis [1].
  • DNA sequences encoding a novel member of the receptor protein tyrosine phosphatase (R-PTP) family, termed PCP-2, were identified in a human pancreatic adenocarcinoma cDNA library [2].
  • Molecular cloning and characterization of a novel human receptor protein tyrosine phosphatase gene, hPTP-J: down-regulation of gene expression by PMA and calcium ionophore in Jurkat T lymphoma cells [3].
  • Synaptopodin expression correlated with the severity of proteinuria and with GLEPP1 expression [4].
  • A PTP produced by the Yersinia bacteria (which can cause bubonic plague, septicemia and enteric diseases) is thought to be used as a 'weapon' against host cell functions [5].

High impact information on PTPRU

  • Structure-function analysis of CD45 and other PTPs has identified structural features of PTP catalytic domains required for enzymatic activity [6].
  • Two members of the Src-family of protein tyrosine kinases (PTKs), the p56lck and p59fyn proteins, have been implicated as physiological substrates of CD45, providing an important clue to how the action of this leukocyte-specific PTP might influence signaling by the T cell antigen receptor [6].
  • The PTP superfamily enzymes, which include tyrosine-specific, dual specificity, low-molecular-weight, and Cdc25 phosphatases, are key mediators of a wide variety of cellular processes, including growth, metabolism, differentiation, motility, and programmed cell death [7].
  • Unlike most members of the PTP superfamily, PTEN utilizes the phosphoinositide second messenger, phosphatidylinositol 3,4,5-trisphosphate (PIP3), as its physiologic substrate [7].
  • Recently, myotubularin, a second PTP superfamily enzyme associated with human disease, has also been shown to utilize a phosphoinositide as its physiologic substrate [7].

Chemical compound and disease context of PTPRU


Biological context of PTPRU

  • Low-molecular-weight protein tyrosine phosphatase (LMW-PTP) is a ubiquitous PTP implicated in the regulation of mitosis and cytoskeleton rearrangement [13].
  • A potential role of PCP-2 in cell-cell recognition and adhesion is supported by its co-localization with cell adhesion molecules, such as catenin and E-cadherin, at sites of cell-cell contact [2].
  • Upon transfection of PCP-2 cDNA into human embryonic kidney fibroblast 293 cells, a protein with an apparent Mr of 180 000 was detected by immunoblot analysis [2].
  • Finally, we showed that PCP-2 was a negative regulator for cell migration [8].
  • This study reports that PCP-2 was endogenously expressed at the cell surface and upregulated with increased cell density [8].

Anatomical context of PTPRU


Associations of PTPRU with chemical compounds

  • A novel PTP, termed protein tyrosine phosphatase receptor omicron (PTPRO), which is related to the homotypically adhering kappa, mu and PCP-2 receptor-type tyrosine phosphatases, was identified and characterized [17].
  • Expression of synaptopodin and GLEPP1 as markers of steroid responsiveness in primary focal segmental glomerulosclerosis [4].
  • The recently cloned type II receptor protein tyrosine phosphatase (RPTP) gene hPTP-J is a new member of the MAM (meprin, A5, PTPmicro) domain subfamily [18].
  • Inhibition of PTP activity through reversible oxidation of the active-site cysteine residue is emerging as a general, yet poorly characterized, regulatory mechanism [19].
  • In conclusion, PTPs are differentially oxidized at physiological pH and H(2)O(2) concentrations, and the PTP loop arginine is an important determinant for susceptibility to oxidation [20].

Physical interactions of PTPRU

  • An in vivo binding assay revealed that PCP-2 could directly interact with beta-catenin through a region in the juxtamembrane domain [8].

Regulatory relationships of PTPRU

  • We here provide evidence that TR-beta 1 but not TR-alpha 1 regulates the expression of the gene coding for PCP-2 in cerebellar Purkinje cells during neonatal rat development and that such regulation appears to be both T3 dependent and T3 independent [21].

Other interactions of PTPRU

  • Thus PTP-LAR appears to play an important role in the maintenance of epithelial integrity, and a loss of its regulatory function may contribute to malignant progression and metastasis [15].
  • In conclusion, interaction of PCP-2 with its substrate beta-catenin is involved in the process of cell-cell contact [8].
  • The receptor-type protein tyrosine phosphatase J antagonizes the biochemical and biological effects of RET-derived oncoproteins [22].
  • RESULTS: There was decreased expression of four DSP genes (including PTEN); eight receptor PTP genes were downregulated in melanoma, among which were PTP-KAPPA and PTP-PI (consistent with our previous data) [23].
  • Synaptopodin, GLEPP1, and nephrin were strongly expressed in normal kidney tissue [24].

Analytical, diagnostic and therapeutic context of PTPRU

  • Molecular cloning and characterization of PTP pi, a novel receptor-like protein-tyrosine phosphatase [25].
  • Site-directed mutagenesis, combined with detailed kinetic and mechanistic studies of Yersinia PTP, have contributed greatly to the understanding of the chemical mechanism for PTP catalysis, the nature of the enzymatic transition state, and the means by which the transition state is stabilized [26].
  • Using degenerate oligonucleotides and the PCR, we have cloned a cDNA for an additional PTP, SH-PTP2, which contains two SH2 domains and is expressed ubiquitously [27].
  • To determine the expression of various protein-tyrosine phosphatases (PTPs) in human gastric cancers, cDNAs encoding conserved PTP domains were amplified by reverse transcriptase polymerase chain reaction from KATO-III cell mRNA and sequenced [28].
  • Guided by x-ray crystallography, molecular modeling, and enzyme kinetic analyses with wild type and mutant PTPs, we describe the development of a general, low molecular weight, non-peptide, non-phosphorus PTP inhibitor into an inhibitor that displays more than 100-fold selectivity for PTPbeta over PTP1B [29].


  1. Association of human protein-tyrosine phosphatase kappa with members of the armadillo family. Fuchs, M., Müller, T., Lerch, M.M., Ullrich, A. J. Biol. Chem. (1996) [Pubmed]
  2. Characterization of PCP-2, a novel receptor protein tyrosine phosphatase of the MAM domain family. Wang, H., Lian, Z., Lerch, M.M., Chen, Z., Xie, W., Ullrich, A. Oncogene (1996) [Pubmed]
  3. Molecular cloning and characterization of a novel human receptor protein tyrosine phosphatase gene, hPTP-J: down-regulation of gene expression by PMA and calcium ionophore in Jurkat T lymphoma cells. Wang, B., Kishihara, K., Zhang, D., Hara, H., Nomoto, K. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  4. Expression of synaptopodin and GLEPP1 as markers of steroid responsiveness in primary focal segmental glomerulosclerosis. Hirakawa, M., Tsuruya, K., Yotsueda, H., Tokumoto, M., Ikeda, H., Katafuchi, R., Fujimi, S., Hirakata, H., Iida, M. Life Sci. (2006) [Pubmed]
  5. Protein tyrosine phosphatases in disease processes. Ninfa, E.G., Dixon, J.E. Trends Cell Biol. (1994) [Pubmed]
  6. CD45: an emerging role as a protein tyrosine phosphatase required for lymphocyte activation and development. Trowbridge, I.S., Thomas, M.L. Annu. Rev. Immunol. (1994) [Pubmed]
  7. PTEN and myotubularin: novel phosphoinositide phosphatases. Maehama, T., Taylor, G.S., Dixon, J.E. Annu. Rev. Biochem. (2001) [Pubmed]
  8. Physical and functional interaction between receptor-like protein tyrosine phosphatase PCP-2 and beta-catenin. Yan, H.X., He, Y.Q., Dong, H., Zhang, P., Zeng, J.Z., Cao, H.F., Wu, M.C., Wang, H.Y. Biochemistry (2002) [Pubmed]
  9. Tyrosine phosphorylation regulates maturation of receptor tyrosine kinases. Schmidt-Arras, D.E., Böhmer, A., Markova, B., Choudhary, C., Serve, H., Böhmer, F.D. Mol. Cell. Biol. (2005) [Pubmed]
  10. Probing protein-tyrosine phosphatase substrate specificity using a phosphotyrosine-containing phage library. Wälchli, S., Espanel, X., Harrenga, A., Rossi, M., Cesareni, G., van Huijsduijnen, R.H. J. Biol. Chem. (2004) [Pubmed]
  11. Crystal structure of the catalytic domain of protein-tyrosine phosphatase SHP-1. Yang, J., Liang, X., Niu, T., Meng, W., Zhao, Z., Zhou, G.W. J. Biol. Chem. (1998) [Pubmed]
  12. Diversity of phytases in the rumen. Nakashima, B.A., McAllister, T.A., Sharma, R., Selinger, L.B. Microb. Ecol. (2007) [Pubmed]
  13. Beta-catenin interacts with low-molecular-weight protein tyrosine phosphatase leading to cadherin-mediated cell-cell adhesion increase. Taddei, M.L., Chiarugi, P., Cirri, P., Buricchi, F., Fiaschi, T., Giannoni, E., Talini, D., Cozzi, G., Formigli, L., Raugei, G., Ramponi, G. Cancer Res. (2002) [Pubmed]
  14. PTPROt: an alternatively spliced and developmentally regulated B-lymphoid phosphatase that promotes G0/G1 arrest. Aguiar, R.C., Yakushijin, Y., Kharbanda, S., Tiwari, S., Freeman, G.J., Shipp, M.A. Blood (1999) [Pubmed]
  15. Phosphorylation and free pool of beta-catenin are regulated by tyrosine kinases and tyrosine phosphatases during epithelial cell migration. Müller, T., Choidas, A., Reichmann, E., Ullrich, A. J. Biol. Chem. (1999) [Pubmed]
  16. Occludin proteolysis and increased permeability in endothelial cells through tyrosine phosphatase inhibition. Wachtel, M., Frei, K., Ehler, E., Fontana, A., Winterhalter, K., Gloor, S.M. J. Cell. Sci. (1999) [Pubmed]
  17. Characterization and chromosomal localization of PTPRO, a novel receptor protein tyrosine phosphatase, expressed in hematopoietic stem cells. Avraham, S., London, R., Tulloch, G.A., Ellis, M., Fu, Y., Jiang, S., White, R.A., Painter, C., Steinberger, A.A., Avraham, H. Gene (1997) [Pubmed]
  18. Transcriptional regulation of a receptor protein tyrosine phosphatase gene hPTP-J by PKC-mediated signaling pathways in Jurkat and Molt-4 T lymphoma cells. Wang, B., Kishihara, K., Zhang, D., Sakamoto, T., Nomoto, K. Biochim. Biophys. Acta (1999) [Pubmed]
  19. Preferential oxidation of the second phosphatase domain of receptor-like PTP-alpha revealed by an antibody against oxidized protein tyrosine phosphatases. Persson, C., Sjöblom, T., Groen, A., Kappert, K., Engström, U., Hellman, U., Heldin, C.H., den Hertog, J., Ostman, A. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  20. Differential oxidation of protein-tyrosine phosphatases. Groen, A., Lemeer, S., van der Wijk, T., Overvoorde, J., Heck, A.J., Ostman, A., Barford, D., Slijper, M., den Hertog, J. J. Biol. Chem. (2005) [Pubmed]
  21. Beta 1 isoform-specific regulation of a triiodothyronine-induced gene during cerebellar development. Strait, K.A., Zou, L., Oppenheimer, J.H. Mol. Endocrinol. (1992) [Pubmed]
  22. The receptor-type protein tyrosine phosphatase J antagonizes the biochemical and biological effects of RET-derived oncoproteins. Iervolino, A., Iuliano, R., Trapasso, F., Viglietto, G., Melillo, R.M., Carlomagno, F., Santoro, M., Fusco, A. Cancer Res. (2006) [Pubmed]
  23. Microarray analysis of phosphatase gene expression in human melanoma. McArdle, L., Rafferty, M.M., Satyamoorthy, K., Maelandsmo, G.M., Dervan, P.A., Herlyn, M., Easty, D.J. Br. J. Dermatol. (2005) [Pubmed]
  24. Podocyte proteins in Galloway-Mowat syndrome. Srivastava, T., Whiting, J.M., Garola, R.E., Dasouki, M.J., Ruotsalainen, V., Tryggvason, K., Hamed, R., Alon, U.S. Pediatr. Nephrol. (2001) [Pubmed]
  25. Molecular cloning and characterization of PTP pi, a novel receptor-like protein-tyrosine phosphatase. Crossland, S., Smith, P.D., Crompton, M.R. Biochem. J. (1996) [Pubmed]
  26. Chemical and mechanistic approaches to the study of protein tyrosine phosphatases. Zhang, Z.Y. Acc. Chem. Res. (2003) [Pubmed]
  27. Identification of a human src homology 2-containing protein-tyrosine-phosphatase: a putative homolog of Drosophila corkscrew. Freeman, R.M., Plutzky, J., Neel, B.G. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  28. Molecular cloning of a human transmembrane-type protein tyrosine phosphatase and its expression in gastrointestinal cancers. Matozaki, T., Suzuki, T., Uchida, T., Inazawa, J., Ariyama, T., Matsuda, K., Horita, K., Noguchi, H., Mizuno, H., Sakamoto, C. J. Biol. Chem. (1994) [Pubmed]
  29. Structure-based design of selective and potent inhibitors of protein-tyrosine phosphatase beta. Lund, I.K., Andersen, H.S., Iversen, L.F., Olsen, O.H., Møller, K.B., Pedersen, A.K., Ge, Y., Holsworth, D.D., Newman, M.J., Axe, F.U., Møller, N.P. J. Biol. Chem. (2004) [Pubmed]
WikiGenes - Universities