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The hunting of the Src

Abstract

The non-receptor tyrosine kinase Src is important for many aspects of cell physiology. The viral src gene was the first retroviral oncogene to be identified, and its cellular counterpart was the first proto-oncogene to be discovered in the vertebrate genome. Src has been important, not only as an object of study in itself, but also as an entry point into the molecular genetics of cancer.

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Figure 1: Memorial symposium in honour of Teruko Hanafusa.
Figure 2: Comparison between v-Src and c-Src.
Figure 3: Activation of c-Src.
Figure 4: Signalling by Src.
Figure 5: Regulation of c-Src by surface receptors.

References

  1. Rous, P. A sarcoma of the fowl transmissible by an agent separable from the tumor cells. J. Exp. Med. 13, 397–411 (1911).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Rubin, H. Quantitative relations between causative virus and cell in the Rous No. 1 chicken sarcoma. Virology 1, 445–473 (1955).

    Article  CAS  PubMed  Google Scholar 

  3. Temin, H. M. & Rubin, H. Characteristics of an assay for Rous sarcoma virus and Rous sarcoma cells in tissue culture. Virology 6, 669–688 (1958).

    Article  CAS  PubMed  Google Scholar 

  4. Halberstaedter, L., Doljanski, L. & Tenenbaum, E. Experiments on the cancerization of cells in vitro by means of Rous sarcoma agent. Brit. J. Exp. Pathol. 22, 179–187 (1941).

    CAS  Google Scholar 

  5. Temin, H. M. The control of cellular morphology in embryonic cells infected with Rous sarcoma virus in vitro. Virology 10, 182–197 (1960).

    Article  CAS  PubMed  Google Scholar 

  6. Rubin, H. & Vogt, P. K. An avian leukosis virus associated with stocks of Rous sarcoma virus. Virology 17, 184–194 (1962).

    Article  CAS  PubMed  Google Scholar 

  7. Hanafusa, H., Hanafusa, T. & Rubin, H. The defectiveness of Rous sarcoma virus. Proc. Natl Acad. Sci. USA 49, 572–580 (1963).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Martin, G. S. Rous sarcoma virus: a function required for the maintenance of the transformed state. Nature 227, 1021–1023 (1970).

    Article  CAS  PubMed  Google Scholar 

  9. Goldé, A. Radio-induced mutants of the Schmidt–Ruppin strain of Rous sarcoma virus. Virology 40, 1022–1029 (1970).

    Article  PubMed  Google Scholar 

  10. Toyoshima, K., Friis, R. R. & Vogt, P. K. The reproductive and cell-transforming capacities of avian sarcoma virus B77: inactivation with UV light. Virology 42, 163–170 (1970).

    Article  CAS  PubMed  Google Scholar 

  11. Duesberg, P. H. & Vogt, P. K. Differences between the ribonucleic acids of transforming and nontransforming avian tumor viruses. Proc. Natl Acad. Sci. USA 67, 1673–1680 (1970).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wang, L. H., Duesberg, P. H., Kawai, S. & Hanafusa, H. Location of envelope-specific and sarcoma-specific oligonucleotides on RNA of Schmidt–Ruppin Rous sarcoma virus. Proc. Natl Acad. Sci. USA 73, 447–451 (1976).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bernstein, A., MacCormick, R. & Martin, G. S. Transformation-defective mutants of avian sarcoma viruses: the genetic relationship between conditional and nonconditional mutants. Virology 70, 206–209 (1976).

    Article  CAS  PubMed  Google Scholar 

  14. Czernilofsky, A. P. et al. Nucleotide sequence of an avian sarcoma virus oncogene (src) and proposed amino acid sequence for gene product. Nature 287, 198–203 (1980).

    Article  CAS  PubMed  Google Scholar 

  15. Czernilofsky, A. P. et al. Corrections to the nucleotide sequence of the src gene of Rous sarcoma virus. Nature 301, 736–738 (1983).

    Article  CAS  PubMed  Google Scholar 

  16. Takeya, T. & Hanafusa, H. DNA sequence of the viral and cellular src gene of chickens. II. Comparison of the src genes of two strains of avian sarcoma virus and of the cellular homolog. J. Virol. 44, 12–18 (1982).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Schwartz, D. E., Tizard, R. & Gilbert, W. Nucleotide sequence of Rous sarcoma virus. Cell 32, 853–869 (1983).

    Article  CAS  PubMed  Google Scholar 

  18. Varmus, H. E., Quintrell, N. & Wyke, J. Revertants of an ASV-transformed rat cell line have lost the complete provius or sustained mutations in src. Virology 108, 28–46 (1981).

    Article  CAS  PubMed  Google Scholar 

  19. Hirai, H. & Varmus, H. E. Mutations in Src homology regions 2 and 3 of activated chicken c-src that result in preferential transformation of mouse or chicken cells. Proc. Natl Acad. Sci. USA 87, 8592–8596 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. DeClue, J. E. & Martin, G. S. Linker insertion-deletion mutagenesis of the v-src gene: isolation of host- and temperature-dependent mutants. J. Virol. 63, 542–554 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Anderson, D. D., Beckmann, R. P., Harms, E. H., Nakamura, K. & Weber, M. J. Biological properties of 'partial' transformation mutants of Rous sarcoma virus and characterization of their pp60src kinase. J. Virol. 37, 445–458 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Weiss, R., Teich, N., Varmus, H. & Coffin, J. RNA Tumor Viruses 2nd edn (Cold Spring Harbor Laboratory, New York, 1984).

    Google Scholar 

  23. Huebner, R. J. & Todaro, G. J. Oncogenes of RNA tumor viruses as determinants of cancer. Proc. Natl Acad. Sci. USA 64, 1087–1094 (1969).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Stehelin, D., Varmus, H. E., Bishop, J. M. & Vogt, P. K. DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA. Nature 260, 170–173 (1976).

    Article  CAS  PubMed  Google Scholar 

  25. Yarden, Y. & Sliwkowski, M. X. Untangling the ErbB signalling network. Nature Rev. Mol. Cell Biol. 2, 127–137 (2001).

    Article  CAS  Google Scholar 

  26. Druker, B. J. et al. Efficacy and safety of a specific inhibitor of the BCR–ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med. 344, 1031–1037 (2001).

    Article  CAS  PubMed  Google Scholar 

  27. Hanafusa, H., Halpern, C. C., Buchhagen, D. L. & Kawai, S. Recovery of avian sarcoma virus from tumors induced by transformation-defective mutants. J. Exp. Med. 146, 1735–1747 (1977).

    Article  CAS  PubMed  Google Scholar 

  28. Takeya, T. & Hanafusa, H. Structure and sequence of the cellular gene homologous to the RSV src gene and the mechanism for generating the transforming virus. Cell 32, 881–890 (1983).

    Article  CAS  PubMed  Google Scholar 

  29. Shalloway, D., Zelenetz, A. D. & Cooper, G. M. Molecular cloning and characterization of the chicken gene homologous to the transforming gene of Rous sarcoma virus. Cell 24, 531–541 (1981).

    Article  CAS  PubMed  Google Scholar 

  30. Parker, R. C., Varmus, H. E. & Bishop, J. H. Expression of v-src and chicken c-src in rat cells demonstrates qualitative differences between pp60v-src and pp60c-src. Cell 37, 131–139 (1984).

    Article  CAS  PubMed  Google Scholar 

  31. Shalloway, D., Coussens, P. M. & Yaciuk, P. Overexpression of the c-src protein does not induce transformation of NIH-3T3 cells. Proc. Natl Acad. Sci. USA 81, 7071–7075 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Iba, H., Takeya, T., Cross, F. R., Hanafusa, T. & Hanafusa, H. Rous sarcoma virus variants that carry the cellular src gene instead of the viral src gene cannot transform chicken embryo fibroblasts. Proc. Natl Acad. Sci. USA 81, 4424–4428 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Johnson, P. J., Coussens, P. M., Danko, A. V. & Shalloway, D. Overexpressed pp60c-src can induce focus formation without complete transformation of NIH-3T3 cells. Mol. Cell. Biol. 5, 1073–1083 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Pawson, T., Martin, G. S. & Smith, A. E. Cell-free translation of virion RNA from nondefective and transformation-defective Rous sarcoma viruses. J. Virol. 19, 950–967 (1976).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Beemon, K. & Hunter, T. In vitro translation yields a possible Rous sarcoma virus src gene product. Proc. Natl Acad. Sci. USA 74, 3302–3306 (1977).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Brugge, J. S. & Erikson, R. L. Identification of a transformation-specific antigen induced by an avian sarcoma virus. Nature 269, 346–348 (1977).

    Article  CAS  PubMed  Google Scholar 

  37. Collett, M. S. & Erikson, R. L. Protein kinase activity associated with the avian sarcoma virus src gene product. Proc. Natl Acad. Sci. USA 75, 2021–2024 (1978).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Levinson, A. D., Oppermann, H., Levintow, L., Varmus, H. E. & Bishop, J. M. Evidence that the transforming gene of avian sarcoma virus encodes a protein kinase associated with a phosphoprotein. Cell 15, 561–572 (1978).

    Article  CAS  PubMed  Google Scholar 

  39. Collett, M. S., Brugge, J. S. & Erikson, R. L. Characterization of a normal avian cell protein related to the avian sarcoma virus transforming gene product. Cell 15, 1363–1369 (1978).

    Article  CAS  PubMed  Google Scholar 

  40. Oppermann, H., Levinson, A. D., Varmus, H. E., Levintow, L. & Bishop, J. M. Uninfected vertebrate cells contain a protein that is closely related to the product of the avian sarcoma virus transforming gene (src). Proc. Natl Acad. Sci. USA 76, 1804–1808 (1979).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Eckhart, W., Hutchinson, M. A. & Hunter, T. An activity phosphorylating tyrosine in polyoma T antigen immunoprecipitates. Cell 18, 925–933 (1979).

    Article  CAS  PubMed  Google Scholar 

  42. Hunter, T. & Sefton, B. M. Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc. Natl Acad. Sci. USA 77, 1311–1315 (1980).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ushiro, H. & Cohen, S. Identification of phosphotyrosine as a product of epidermal growth factor-activated protein kinase in A-431 cell membranes. J. Biol. Chem. 255, 8363–8365 (1980).

    CAS  PubMed  Google Scholar 

  44. Smart, J. E. et al. Characterization of sites for tyrosine phosphorylation in the transforming protein of Rous sarcoma virus (pp60v-src) and its normal cellular homologue (pp60c-src). Proc. Natl Acad. Sci. USA 78, 6013–6017 (1981).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Patschinsky, T., Hunter, T., Esch, F. S., Cooper, J. A. & Sefton, B. M. Analysis of the sequence of amino acids surrounding sites of tyrosine phosphorylation. Proc. Natl Acad. Sci. USA 79, 973–977 (1982).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Bolen, J. B. et al. Enhancement of cellular src gene product associated tyrosyl kinase activity following polyoma virus infection and transformation. Cell 38, 767–777 (1984).

    Article  CAS  PubMed  Google Scholar 

  47. Courtneidge, S. A. Activation of the pp60c-src kinase by middle T antigen binding or by dephosphorylation. EMBO J. 4, 1471–1477 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Cooper, J. A., Gould, K. L., Cartwright, C. A. & Hunter, T. Tyr527 is phosphorylated in pp60c-src: implications for regulation. Science 231, 1431–1434 (1986).

    Article  CAS  PubMed  Google Scholar 

  49. Kmiecik, T. E. & Shalloway, D. Activation and suppression of pp60c-src transforming ability by mutation of its primary sites of tyrosine phosphorylation. Cell 49, 65–73 (1987).

    Article  CAS  PubMed  Google Scholar 

  50. Cartwright, C. A., Eckhart, W., Simon, S. & Kaplan, P. L. Cell transformation by pp60c-src mutated in the carboxy-terminal regulatory domain. Cell 49, 83–91 (1987).

    Article  CAS  PubMed  Google Scholar 

  51. Piwnica-Worms, H., Saunders, K. B., Roberts, T. M., Smith, A. E. & Cheng, S. H. Tyrosine phosphorylation regulates the biochemical and biological properties of pp60c-src. Cell 49, 75–82 (1987).

    Article  CAS  PubMed  Google Scholar 

  52. Okada, M. & Nakagawa, H. A protein tyrosine kinase involved in regulation of pp60c-src function. J. Biol. Chem. 264, 20886–20893 (1989).

    CAS  PubMed  Google Scholar 

  53. Duesberg, P. et al. Persistent Viruses (eds Stevens, J. G. et al.) 245–266 (Academic Press, New York, 1978).

    Google Scholar 

  54. Stone, J. C., Atkinson, T., Smith, M. & Pawson, T. Identification of functional regions in the transforming protein of Fujinami sarcoma virus by in-phase insertion mutagenesis. Cell 37, 549–558 (1984).

    Article  CAS  PubMed  Google Scholar 

  55. Sadowski, I., Stone, J. C. & Pawson, T. A noncatalytic domain conserved among cytoplasmic protein-tyrosine kinases modifies the kinase function and transforming activity of Fujinami sarcoma virus P130gag-fps. Mol. Cell. Biol. 6, 4396–4408 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Moran, M. F. et al. Src homology region 2 domains direct protein–protein interactions in signal transduction. Proc. Natl Acad. Sci. USA 87, 8622–8626 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Matsuda, M., Mayer, B. J., Fukui, Y. & Hanafusa, H. Binding of transforming protein, P47gag-crk, to a broad range of phosphotyrosine-containing proteins. Science 248, 1537–1539 (1990).

    Article  CAS  PubMed  Google Scholar 

  58. Mayer, B. J., Hamaguchi, M. & Hanafusa, H. A novel viral oncogene with structural similarity to phospholipase C. Nature 332, 272–275 (1988).

    Article  CAS  PubMed  Google Scholar 

  59. Ren, R., Mayer, B. J., Cicchetti, P. & Baltimore, D. Identification of a ten-amino acid proline-rich SH3 binding site. Science 259, 1157–1161 (1993).

    Article  CAS  PubMed  Google Scholar 

  60. Roussel, R. R., Brodeur, S. R., Shalloway, D. & Laudano, A. P. Selective binding of activated pp60c-src by an immobilized synthetic phosphopeptide modeled on the carboxyl terminus of pp60c-src. Proc. Natl Acad. Sci. USA 88, 10696–10700 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Liu, X. et al. Regulation of c-Src tyrosine kinase activity by the Src SH2 domain. Oncogene 8, 1119–1126 (1993).

    CAS  PubMed  Google Scholar 

  62. Murphy, S. M., Bergman, M. & Morgan, D. O. Suppression of c-Src activity by C-terminal Src kinase involves the c-Src SH2 and SH3 domains: analysis with Saccharomyces cerevisiae. Mol. Cell. Biol. 13, 5290–5300 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Superti-Furga, G., Fumagalli, S., Koegl, M., Courtneidge, S. A. & Draetta, G. Csk inhibition of c-Src activity requires both the SH2 and SH3 domains of Src. EMBO J. 12, 2625–2634 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Okada, M., Howell, B. W., Broome, M. A. & Cooper, J. A. Deletion of the SH3 domain of Src interferes with regulation by the phosphorylated carboxyl-terminal tyrosine. J. Biol. Chem. 268, 18070–18075 (1993).

    CAS  PubMed  Google Scholar 

  65. Sicheri, F., Moarefi, I. & Kuriyan, J. Crystal structure of the Src family tyrosine kinase Hck. Nature 385, 602–609 (1997).

    Article  CAS  PubMed  Google Scholar 

  66. Xu, W., Harrison, S. C. & Eck, M. J. Three-dimensional structure of the tyrosine kinase c-Src. Nature 385, 595–602 (1997).

    Article  CAS  PubMed  Google Scholar 

  67. Xu, W., Doshi, A., Lei, M., Eck, M. J. & Harrison, S. C. Crystal structures of c-Src reveal features of its autoinhibitory mechanism. Mol. Cell 3, 629–638 (1999).

    Article  CAS  PubMed  Google Scholar 

  68. Schindler, T. et al. Crystal structure of Hck in complex with a Src family-selective tyrosine kinase inhibitor. Mol. Cell 3, 639–648 (1999).

    Article  CAS  PubMed  Google Scholar 

  69. Young, M. A., Gonfloni, S., Superti-Furga, G., Roux, B. & Kuriyan, J. Dynamic coupling between the SH2 and SH3 domains of c-Src and Hck underlies their inactivation by C-terminal tyrosine phosphorylation. Cell 105, 115–126 (2001).

    Article  CAS  PubMed  Google Scholar 

  70. Ambros, V. R., Chen, L. B. & Buchanan, J. M. Surface ruffles as markers for studies of cell transformation by Rous sarcoma virus. Proc. Natl Acad. Sci. USA 72, 3144–3148 (1975).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Beug, H., Claviez, M., Jockusch, B. M. & Graf, T. Differential expression of Rous Sarcoma virus-specific transformation parameters in enucleated cells. Cell 14, 843–856 (1978).

    Article  CAS  PubMed  Google Scholar 

  72. Groudine, M. & Weintraub, H. Activation of cellular genes by avian RNA tumor viruses. Proc. Natl Acad. Sci. USA 77, 5351–5354 (1980).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Erikson, E. & Erikson, R. L. Identification of a cellular protein substrate phosphorylated by the avian sarcoma virus-transforming gene product. Cell 21, 829–836 (1980).

    Article  CAS  PubMed  Google Scholar 

  74. Radke, K. & Martin, G. S. Transformation by Rous sarcoma virus: effects of src gene expression on the synthesis and phosphorylation of cellular polypeptides. Proc. Natl Acad. Sci. USA 76, 5212–5216 (1979).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Cooper, J. A. & Hunter, T. Changes in protein phosphorylation in Rous sarcoma virus-transformed chicken embryo cells. Mol. Cell. Biol. 1, 165–178 (1981).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Ross, A. H., Baltimore, D. & Eisen, H. N. Phosphotyrosine-containing proteins isolated by affinity chromatography with antibodies to a synthetic hapten. Nature 294, 654–656 (1981).

    Article  CAS  PubMed  Google Scholar 

  77. Frackelton, A. R. Jr., Ross, A. H. & Eisen, H. N. Characterization and use of monoclonal antibodies for isolation of phosphotyrosyl proteins from retrovirus-transformed cells and growth factor-stimulated cells. Mol. Cell. Biol. 3, 1343–1352 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Kanner, S. B., Reynolds, A. B. & Parsons, J. T. Immunoaffinity purification of tyrosine-phosphorylated cellular proteins. J. Immunol. Methods 120, 115–124 (1989).

    Article  CAS  PubMed  Google Scholar 

  79. Lipfert, L. et al. Integrin-dependent phosphorylation and activation of the protein tyrosine kinase pp125FAK in platelets. J. Cell Biol. 119, 905–912 (1992).

    Article  CAS  PubMed  Google Scholar 

  80. Sakai, R. et al. A novel signaling molecule, p130, forms stable complexes in vivo with v-Crk and v-Src in a tyrosine phosphorylation-dependent manner. EMBO J. 13, 3748–3756 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Shah, K., Liu, Y., Deirmengian, C. & Shokat, K. M. Engineering unnatural nucleotide specificity for Rous sarcoma virus tyrosine kinase to uniquely label its direct substrates. Proc. Natl Acad. Sci. USA 94, 3565–3570 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Sugimoto, Y., Whitman, M., Cantley, L. C. & Erikson, R. L. Evidence that the Rous sarcoma virus transforming gene product phosphorylates phosphatidylinositol and diacylglycerol. Proc. Natl Acad. Sci. USA 81, 2117–2121 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Macara, I. G., Marinetti, G. V. & Balduzzi, P. C. Transforming protein of avian sarcoma virus UR2 is associated with phosphatidylinositol kinase activity: possible role in tumorigenesis. Proc. Natl Acad. Sci. USA 81, 2728–2732 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Whitman, M., Downes, C. P., Keeler, M., Keller, T. & Cantley, L. Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate. Nature 332, 644–646 (1988).

    Article  CAS  PubMed  Google Scholar 

  85. Smith, M. R., DeGudicibus, S. J. & Stacey, D. W. Requirement for c-ras proteins during viral oncogene transformation. Nature 320, 540–543 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Aftab, D. T., Kwan, J. & Martin, G. S. Ras-independent transformation by v-Src. Proc. Natl Acad. Sci. USA 94, 3028–3033 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Penuel, E. & Martin, G. S. Transformation by v-Src: Ras-MAPK and PI3K-mTOR mediate parallel pathways. Mol. Biol. Cell 10, 1693–1703 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Yu, C. L. et al. Enhanced DNA-binding activity of a Stat3-related protein in cells transformed by the Src oncoprotein. Science 269, 81–83 (1995).

    Article  CAS  PubMed  Google Scholar 

  89. Turkson, J. et al. Stat3 activation by Src induces specific gene regulation and is required for cell transformation. Mol. Cell. Biol. 18, 2545–2552 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Bromberg, J. F., Horvath, C. M., Besser, D., Lathem, W. W. & Darnell, J. E. Jr Stat3 activation is required for cellular transformation by v-src. Mol. Cell. Biol. 18, 2553–2558 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Bromberg, J. F. et al. Stat3 as an oncogene. Cell 98, 295–303 (1999).

    Article  CAS  PubMed  Google Scholar 

  92. Ralston, R. & Bishop, J. M. The product of the protooncogene c-src is modified during the cellular response to platelet-derived growth factor. Proc. Natl Acad. Sci. USA 82, 7845–7849 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Gould, K. L. & Hunter, T. Platelet-derived growth factor induces multisite phosphorylation of pp60c-src and increases its protein-tyrosine kinase activity. Mol. Cell. Biol. 8, 3345–3356 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Kypta, R. M., Goldberg, Y., Ulug, E. T. & Courtneidge, S. A. Association between the PDGF receptor and members of the src family of tyrosine kinases. Cell 62, 481–492 (1990).

    Article  CAS  PubMed  Google Scholar 

  95. Twamley-Stein, G. M., Pepperkok, R., Ansorge, W. & Courtneidge, S. A. The Src family tyrosine kinases are required for platelet-derived growth factor-mediated signal transduction in NIH 3T3 cells. Proc. Natl Acad. Sci. USA 90, 7696–7700 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Chackalaparampil, I. & Shalloway, D. Altered phosphorylation and activation of pp60c-src during fibroblast mitosis. Cell 52, 801–810 (1988).

    Article  CAS  PubMed  Google Scholar 

  97. Roche, S., Fumagalli, S. & Courtneidge, S. A. Requirement for Src family protein tyrosine kinases in G2 for fibroblast cell division. Science 269, 1567–1569 (1995).

    Article  CAS  PubMed  Google Scholar 

  98. Cotton, P. C. & Brugge, J. S. Neural tissues express high levels of the cellular src gene product pp60c-src. Mol. Cell. Biol. 3, 1157–1162 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Golden, A., Nemeth, S. P. & Brugge, J. S. Blood platelets express high levels of the pp60c-src-specific tyrosine kinase activity. Proc. Natl Acad. Sci. USA 83, 852–856 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Rohrschneider, L. R. Adhesion plaques of Rous sarcoma virus-transformed cells contain the src gene product. Proc. Natl Acad. Sci. USA 77, 351–358 (1980).

    Article  Google Scholar 

  101. Ferrell, J. E. Jr & Martin, G. S. Tyrosine-specific protein phosphorylation is regulated by glycoprotein IIb–IIIa in platelets. Proc. Natl Acad. Sci. USA 86, 2234–2238 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Golden, A., Brugge, J. S. & Shattil, S. J. Role of platelet membrane glycoprotein IIb–IIIa in agonist-induced tyrosine phosphorylation of platelet proteins. J. Cell. Biol. 111, 3117–3127 (1990).

    Article  CAS  PubMed  Google Scholar 

  103. Soriano, P., Montgomery, C., Geske, R. & Bradley, A. Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell 64, 693–702 (1991).

    Article  CAS  PubMed  Google Scholar 

  104. Stein, P. L., Vogel, H. & Soriano, P. Combined deficiencies of Src, Fyn, and Yes tyrosine kinases in mutant mice. Genes Dev. 8, 1999–2007 (1994).

    Article  CAS  PubMed  Google Scholar 

  105. Klinghoffer, R. A., Sachsenmaier, C., Cooper, J. A. & Soriano, P. Src family kinases are required for integrin but not PDGFR signal transduction. EMBO J. 18, 2459–2471 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Broome, M. A. & Courtneidge, S. A. No requirement for src family kinases for PDGF signaling in fibroblasts expressing SV40 large T antigen. Oncogene 19, 2867–2869 (2000).

    Article  CAS  PubMed  Google Scholar 

  107. Thomas, S. M. & Brugge, J. S. Cellular functions regulated by Src family kinases. Annu. Rev. Cell. Dev. Biol. 13, 513–609 (1997).

    Article  CAS  PubMed  Google Scholar 

  108. Brown, M. T. & Cooper, J. A. Regulation, substrates and functions of src. Biochim. Biophys. Acta 1287, 121–149 (1996).

    PubMed  Google Scholar 

  109. Bjorge, J. D., Jakymiw, A. & Fujita, D. J. Selected glimpses into the activation and function of Src kinase. Oncogene 19, 5620–5635 (2000).

    Article  CAS  PubMed  Google Scholar 

  110. Abram, C. L. & Courtneidge, S. A. Src family tyrosine kinases and growth factor signaling. Exp. Cell Res. 254, 1–13 (2000).

    Article  CAS  PubMed  Google Scholar 

  111. Luttrell, L. M. et al. β-arrestin-dependent formation of β2 adrenergic receptor-Src protein kinase complexes. Science 283, 655–661 (1999).

    Article  CAS  PubMed  Google Scholar 

  112. Wong, B. R. et al. TRANCE, a TNF family member, activates Akt/PKB through a signaling complex involving TRAF6 and c-Src. Mol. Cell 4, 1041–1049 (1999).

    Article  CAS  PubMed  Google Scholar 

  113. Maller, J. L. The elusive progesterone receptor in Xenopus oocytes. Proc. Natl Acad. Sci. USA 98, 8–10 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Jacobs, C. & Rubsamen, H. Expression of pp60c-src protein kinase in adult and fetal human tissue: high activities in some sarcomas and mammary carcinomas. Cancer Res. 43, 1696–1702 (1983).

    CAS  PubMed  Google Scholar 

  115. Luttrell, D. K., Luttrell, L. M. & Parsons, S. J. Augmented mitogenic responsiveness to epidermal growth factor in murine fibroblasts that overexpress pp60c-src. Mol. Cell. Biol. 8, 497–501 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Bowman, T., Garcia, R., Turkson, J. & Jove, R. STATs in oncogenesis. Oncogene 19, 2474–2488 (2000).

    Article  CAS  PubMed  Google Scholar 

  117. Bolen, J. B., Veillette, A., Schwartz, A. M., DeSeau, V. & Rosen, N. Activation of pp60c-src protein kinase activity in human colon carcinoma. Proc. Natl Acad. Sci. USA 84, 2251–2255 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Cartwright, C. A., Meisler, A. I. & Eckhart, W. Activation of the pp60c-src protein kinase is an early event in colonic carcinogenesis. Proc. Natl Acad. Sci. USA 87, 558–562 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Irby, R. B. et al. Activating SRC mutation in a subset of advanced human colon cancers. Nature Genet. 21, 187–190 (1999).

    Article  CAS  PubMed  Google Scholar 

  120. Blake, R. A. et al. SU6656, a selective src family kinase inhibitor, used to probe growth factor signaling. Mol. Cell. Biol. 20, 9018–9027 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

I thank S. Taylor, M. Botchan, J. Brugge and T. Hunter for helpful comments on the manuscript.

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Authors and Affiliations

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DATABASE LINKS

c-src

EGFR

Csk

Fps

crk

phospholipase Cγ

Hck

annexin II

FAK

Cas

Shc

Stat3

MAPK

MEK

JAK

Btk

PDGF

c-myc

fibrinogen

osteopetrosis

Lck

Blk

Fgr

Lyn

Yes

β-adrenergic receptor

TRANCE

PTPα

progesterone receptor

p190

paxillin

cortactin

β-catenin

p120

plakoglobin

FURTHER INFORMATION

Martin lab

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Martin, G. The hunting of the Src. Nat Rev Mol Cell Biol 2, 467–475 (2001). https://doi.org/10.1038/35073094

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  • DOI: https://doi.org/10.1038/35073094

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