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. 1992 Dec 1;89(23):11239–11243. doi: 10.1073/pnas.89.23.11239

Identification of a human src homology 2-containing protein-tyrosine-phosphatase: a putative homolog of Drosophila corkscrew.

R M Freeman Jr 1, J Plutzky 1, B G Neel 1
PMCID: PMC50525  PMID: 1280823

Abstract

src homology 2 (SH2) domains direct binding to specific phosphotyrosyl proteins. Recently, SH2-containing protein-tyrosine-phosphatases (PTPs) were identified. 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. When expressed in Escherichia coli, SH-PTP2 displays tyrosine-specific phosphatase activity. Strong sequence similarity between SH-PTP2 and the Drosophila gene corkscrew (csw) and their similar patterns of expression suggest that SH-PTP2 is the human corkscrew homolog. Sequence comparisons between SH-PTP2, SH-PTP1, corkscrew, and other SH2-containing proteins suggest the existence of a subfamily of SH2 domains found specifically in PTPs, whereas comparison of the PTP domains of the SH2-containing PTPs with other tyrosine phosphatases suggests the existence of a subfamily of PTPs containing SH2 domains. Since corkscrew, a member of the terminal class signal transduction pathway, acts in concert with D-raf to positively transduce the signal generated by the receptor tyrosine kinase torso, these findings suggest several mechanisms by which SH-PTP2 may participate in mammalian signal transduction.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  2. Ambrosio L., Mahowald A. P., Perrimon N. Requirement of the Drosophila raf homologue for torso function. Nature. 1989 Nov 16;342(6247):288–291. doi: 10.1038/342288a0. [DOI] [PubMed] [Google Scholar]
  3. App H., Hazan R., Zilberstein A., Ullrich A., Schlessinger J., Rapp U. Epidermal growth factor (EGF) stimulates association and kinase activity of Raf-1 with the EGF receptor. Mol Cell Biol. 1991 Feb;11(2):913–919. doi: 10.1128/mcb.11.2.913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baccarini M., Sabatini D. M., App H., Rapp U. R., Stanley E. R. Colony stimulating factor-1 (CSF-1) stimulates temperature dependent phosphorylation and activation of the RAF-1 proto-oncogene product. EMBO J. 1990 Nov;9(11):3649–3657. doi: 10.1002/j.1460-2075.1990.tb07576.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bishop J. M. Molecular themes in oncogenesis. Cell. 1991 Jan 25;64(2):235–248. doi: 10.1016/0092-8674(91)90636-d. [DOI] [PubMed] [Google Scholar]
  6. Brown-Shimer S., Johnson K. A., Lawrence J. B., Johnson C., Bruskin A., Green N. R., Hill D. E. Molecular cloning and chromosome mapping of the human gene encoding protein phosphotyrosyl phosphatase 1B. Proc Natl Acad Sci U S A. 1990 Jul;87(13):5148–5152. doi: 10.1073/pnas.87.13.5148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brönner G., Jäckle H. Control and function of terminal gap gene activity in the posterior pole region of the Drosophila embryo. Mech Dev. 1991 Nov;35(3):205–211. doi: 10.1016/0925-4773(91)90019-3. [DOI] [PubMed] [Google Scholar]
  8. Cantley L. C., Auger K. R., Carpenter C., Duckworth B., Graziani A., Kapeller R., Soltoff S. Oncogenes and signal transduction. Cell. 1991 Jan 25;64(2):281–302. doi: 10.1016/0092-8674(91)90639-g. [DOI] [PubMed] [Google Scholar]
  9. Casanova J., Struhl G. Localized surface activity of torso, a receptor tyrosine kinase, specifies terminal body pattern in Drosophila. Genes Dev. 1989 Dec;3(12B):2025–2038. doi: 10.1101/gad.3.12b.2025. [DOI] [PubMed] [Google Scholar]
  10. Chabot B., Stephenson D. A., Chapman V. M., Besmer P., Bernstein A. The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus. Nature. 1988 Sep 1;335(6185):88–89. doi: 10.1038/335088a0. [DOI] [PubMed] [Google Scholar]
  11. Charbonneau H., Tonks N. K., Walsh K. A., Fischer E. H. The leukocyte common antigen (CD45): a putative receptor-linked protein tyrosine phosphatase. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7182–7186. doi: 10.1073/pnas.85.19.7182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Chernoff J., Schievella A. R., Jost C. A., Erikson R. L., Neel B. G. Cloning of a cDNA for a major human protein-tyrosine-phosphatase. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2735–2739. doi: 10.1073/pnas.87.7.2735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Cool D. E., Tonks N. K., Charbonneau H., Walsh K. A., Fischer E. H., Krebs E. G. cDNA isolated from a human T-cell library encodes a member of the protein-tyrosine-phosphatase family. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5257–5261. doi: 10.1073/pnas.86.14.5257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dingwall C., Laskey R. A. Protein import into the cell nucleus. Annu Rev Cell Biol. 1986;2:367–390. doi: 10.1146/annurev.cb.02.110186.002055. [DOI] [PubMed] [Google Scholar]
  16. Escobedo J. A., Navankasattusas S., Kavanaugh W. M., Milfay D., Fried V. A., Williams L. T. cDNA cloning of a novel 85 kd protein that has SH2 domains and regulates binding of PI3-kinase to the PDGF beta-receptor. Cell. 1991 Apr 5;65(1):75–82. doi: 10.1016/0092-8674(91)90409-r. [DOI] [PubMed] [Google Scholar]
  17. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  18. Fischer E. H., Charbonneau H., Tonks N. K. Protein tyrosine phosphatases: a diverse family of intracellular and transmembrane enzymes. Science. 1991 Jul 26;253(5018):401–406. doi: 10.1126/science.1650499. [DOI] [PubMed] [Google Scholar]
  19. Gebert J. F., Moghal N., Frangioni J. V., Sugarbaker D. J., Neel B. G. High frequency of retinoic acid receptor beta abnormalities in human lung cancer. Oncogene. 1991 Oct;6(10):1859–1868. [PubMed] [Google Scholar]
  20. Geissler E. N., Ryan M. A., Housman D. E. The dominant-white spotting (W) locus of the mouse encodes the c-kit proto-oncogene. Cell. 1988 Oct 7;55(1):185–192. doi: 10.1016/0092-8674(88)90020-7. [DOI] [PubMed] [Google Scholar]
  21. Gu M. X., York J. D., Warshawsky I., Majerus P. W. Identification, cloning, and expression of a cytosolic megakaryocyte protein-tyrosine-phosphatase with sequence homology to cytoskeletal protein 4.1. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5867–5871. doi: 10.1073/pnas.88.13.5867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Horvitz H. R., Sternberg P. W. Multiple intercellular signalling systems control the development of the Caenorhabditis elegans vulva. Nature. 1991 Jun 13;351(6327):535–541. doi: 10.1038/351535a0. [DOI] [PubMed] [Google Scholar]
  23. Hunter T. Cooperation between oncogenes. Cell. 1991 Jan 25;64(2):249–270. doi: 10.1016/0092-8674(91)90637-e. [DOI] [PubMed] [Google Scholar]
  24. Jones S. W., Erikson R. L., Ingebritsen V. M., Ingebritsen T. S. Phosphotyrosyl-protein phosphatases. I. Separation of multiple forms from bovine brain and purification of the major form to near homogeneity. J Biol Chem. 1989 May 5;264(13):7747–7753. [PubMed] [Google Scholar]
  25. Kaplan D. R., Morrison D. K., Wong G., McCormick F., Williams L. T. PDGF beta-receptor stimulates tyrosine phosphorylation of GAP and association of GAP with a signaling complex. Cell. 1990 Apr 6;61(1):125–133. doi: 10.1016/0092-8674(90)90220-9. [DOI] [PubMed] [Google Scholar]
  26. Kemp B. E., Pearson R. B. Protein kinase recognition sequence motifs. Trends Biochem Sci. 1990 Sep;15(9):342–346. doi: 10.1016/0968-0004(90)90073-k. [DOI] [PubMed] [Google Scholar]
  27. Kennelly P. J., Krebs E. G. Consensus sequences as substrate specificity determinants for protein kinases and protein phosphatases. J Biol Chem. 1991 Aug 25;266(24):15555–15558. [PubMed] [Google Scholar]
  28. Koch C. A., Anderson D., Moran M. F., Ellis C., Pawson T. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science. 1991 May 3;252(5006):668–674. doi: 10.1126/science.1708916. [DOI] [PubMed] [Google Scholar]
  29. Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell. 1986 Jan 31;44(2):283–292. doi: 10.1016/0092-8674(86)90762-2. [DOI] [PubMed] [Google Scholar]
  30. Krueger N. X., Streuli M., Saito H. Structural diversity and evolution of human receptor-like protein tyrosine phosphatases. EMBO J. 1990 Oct;9(10):3241–3252. doi: 10.1002/j.1460-2075.1990.tb07523.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  32. Li P., Wood K., Mamon H., Haser W., Roberts T. Raf-1: a kinase currently without a cause but not lacking in effects. Cell. 1991 Feb 8;64(3):479–482. doi: 10.1016/0092-8674(91)90228-q. [DOI] [PubMed] [Google Scholar]
  33. Margolis B., Rhee S. G., Felder S., Mervic M., Lyall R., Levitzki A., Ullrich A., Zilberstein A., Schlessinger J. EGF induces tyrosine phosphorylation of phospholipase C-II: a potential mechanism for EGF receptor signaling. Cell. 1989 Jun 30;57(7):1101–1107. doi: 10.1016/0092-8674(89)90047-0. [DOI] [PubMed] [Google Scholar]
  34. Matthews R. J., Bowne D. B., Flores E., Thomas M. L. Characterization of hematopoietic intracellular protein tyrosine phosphatases: description of a phosphatase containing an SH2 domain and another enriched in proline-, glutamic acid-, serine-, and threonine-rich sequences. Mol Cell Biol. 1992 May;12(5):2396–2405. doi: 10.1128/mcb.12.5.2396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Matthews R. J., Cahir E. D., Thomas M. L. Identification of an additional member of the protein-tyrosine-phosphatase family: evidence for alternative splicing in the tyrosine phosphatase domain. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4444–4448. doi: 10.1073/pnas.87.12.4444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Meisenhelder J., Suh P. G., Rhee S. G., Hunter T. Phospholipase C-gamma is a substrate for the PDGF and EGF receptor protein-tyrosine kinases in vivo and in vitro. Cell. 1989 Jun 30;57(7):1109–1122. doi: 10.1016/0092-8674(89)90048-2. [DOI] [PubMed] [Google Scholar]
  37. Morrison D. K., Kaplan D. R., Escobedo J. A., Rapp U. R., Roberts T. M., Williams L. T. Direct activation of the serine/threonine kinase activity of Raf-1 through tyrosine phosphorylation by the PDGF beta-receptor. Cell. 1989 Aug 25;58(4):649–657. doi: 10.1016/0092-8674(89)90100-1. [DOI] [PubMed] [Google Scholar]
  38. Morrison D. K., Kaplan D. R., Rapp U., Roberts T. M. Signal transduction from membrane to cytoplasm: growth factors and membrane-bound oncogene products increase Raf-1 phosphorylation and associated protein kinase activity. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8855–8859. doi: 10.1073/pnas.85.23.8855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Newport J. W., Forbes D. J. The nucleus: structure, function, and dynamics. Annu Rev Biochem. 1987;56:535–565. doi: 10.1146/annurev.bi.56.070187.002535. [DOI] [PubMed] [Google Scholar]
  40. Otsu M., Hiles I., Gout I., Fry M. J., Ruiz-Larrea F., Panayotou G., Thompson A., Dhand R., Hsuan J., Totty N. Characterization of two 85 kd proteins that associate with receptor tyrosine kinases, middle-T/pp60c-src complexes, and PI3-kinase. Cell. 1991 Apr 5;65(1):91–104. doi: 10.1016/0092-8674(91)90411-q. [DOI] [PubMed] [Google Scholar]
  41. Pendergast A. M., Muller A. J., Havlik M. H., Maru Y., Witte O. N. BCR sequences essential for transformation by the BCR-ABL oncogene bind to the ABL SH2 regulatory domain in a non-phosphotyrosine-dependent manner. Cell. 1991 Jul 12;66(1):161–171. doi: 10.1016/0092-8674(91)90148-r. [DOI] [PubMed] [Google Scholar]
  42. Perkins L. A., Larsen I., Perrimon N. corkscrew encodes a putative protein tyrosine phosphatase that functions to transduce the terminal signal from the receptor tyrosine kinase torso. Cell. 1992 Jul 24;70(2):225–236. doi: 10.1016/0092-8674(92)90098-w. [DOI] [PubMed] [Google Scholar]
  43. Pignoni F., Baldarelli R. M., Steingrímsson E., Diaz R. J., Patapoutian A., Merriam J. R., Lengyel J. A. The Drosophila gene tailless is expressed at the embryonic termini and is a member of the steroid receptor superfamily. Cell. 1990 Jul 13;62(1):151–163. doi: 10.1016/0092-8674(90)90249-e. [DOI] [PubMed] [Google Scholar]
  44. Plutzky J., Neel B. G., Rosenberg R. D. Isolation of a src homology 2-containing tyrosine phosphatase. Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):1123–1127. doi: 10.1073/pnas.89.3.1123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Rapp U. R. Role of Raf-1 serine/threonine protein kinase in growth factor signal transduction. Oncogene. 1991 Apr;6(4):495–500. [PubMed] [Google Scholar]
  46. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Shen S. H., Bastien L., Posner B. I., Chrétien P. A protein-tyrosine phosphatase with sequence similarity to the SH2 domain of the protein-tyrosine kinases. Nature. 1991 Aug 22;352(6337):736–739. doi: 10.1038/352736a0. [DOI] [PubMed] [Google Scholar]
  48. Skolnik E. Y., Margolis B., Mohammadi M., Lowenstein E., Fischer R., Drepps A., Ullrich A., Schlessinger J. Cloning of PI3 kinase-associated p85 utilizing a novel method for expression/cloning of target proteins for receptor tyrosine kinases. Cell. 1991 Apr 5;65(1):83–90. doi: 10.1016/0092-8674(91)90410-z. [DOI] [PubMed] [Google Scholar]
  49. Sprenger F., Stevens L. M., Nüsslein-Volhard C. The Drosophila gene torso encodes a putative receptor tyrosine kinase. Nature. 1989 Apr 6;338(6215):478–483. doi: 10.1038/338478a0. [DOI] [PubMed] [Google Scholar]
  50. St Johnston D., Nüsslein-Volhard C. The origin of pattern and polarity in the Drosophila embryo. Cell. 1992 Jan 24;68(2):201–219. doi: 10.1016/0092-8674(92)90466-p. [DOI] [PubMed] [Google Scholar]
  51. Streuli M., Krueger N. X., Hall L. R., Schlossman S. F., Saito H. A new member of the immunoglobulin superfamily that has a cytoplasmic region homologous to the leukocyte common antigen. J Exp Med. 1988 Nov 1;168(5):1523–1530. doi: 10.1084/jem.168.5.1523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Streuli M., Krueger N. X., Thai T., Tang M., Saito H. Distinct functional roles of the two intracellular phosphatase like domains of the receptor-linked protein tyrosine phosphatases LCA and LAR. EMBO J. 1990 Aug;9(8):2399–2407. doi: 10.1002/j.1460-2075.1990.tb07415.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Streuli M., Krueger N. X., Tsai A. Y., Saito H. A family of receptor-linked protein tyrosine phosphatases in humans and Drosophila. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8698–8702. doi: 10.1073/pnas.86.22.8698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Waksman G., Kominos D., Robertson S. C., Pant N., Baltimore D., Birge R. B., Cowburn D., Hanafusa H., Mayer B. J., Overduin M. Crystal structure of the phosphotyrosine recognition domain SH2 of v-src complexed with tyrosine-phosphorylated peptides. Nature. 1992 Aug 20;358(6388):646–653. doi: 10.1038/358646a0. [DOI] [PubMed] [Google Scholar]
  55. Yang Q., Tonks N. K. Isolation of a cDNA clone encoding a human protein-tyrosine phosphatase with homology to the cytoskeletal-associated proteins band 4.1, ezrin, and talin. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):5949–5953. doi: 10.1073/pnas.88.14.5949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Yi T. L., Cleveland J. L., Ihle J. N. Protein tyrosine phosphatase containing SH2 domains: characterization, preferential expression in hematopoietic cells, and localization to human chromosome 12p12-p13. Mol Cell Biol. 1992 Feb;12(2):836–846. doi: 10.1128/mcb.12.2.836. [DOI] [PMC free article] [PubMed] [Google Scholar]

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