Interaction of the Rous Sarcoma Virus Protein pp60src with the Cellular Proteins pp50 and pp90

  • J. S. Brugge
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 123)


Oncogenic retroviruses cause multiple and profound alterations in the morphology, metabolism, and growth control of cells. In most retrovirus infected cells, all of these complex changes in the cellular phenotype are mediated by a single virus-encoded gene product, referred to as the transforming protein. Rous sarcoma virus (RSV) has proven to be an ideal system for the analysis of events which occur following oncogenic transformation by retroviruses. RSV induces rapid sarcoma production after injection of virus in vivo and efficient and rapid transformation of cells in culture (HANAFUSA 1977). The transforming gene of RSV encodes a protein of Mr 60 000 which has been designated pp60 src (Brugge and Erikson 1977; Purchio et al. 1978). Genetic studies of viruses encoding mutant src gene products which induce a partially transformed phenotype suggest that interactions between pp60 src and multiple cellular targets are required to elicit a fully transformed phenotype (review, Sefton and Hunter 1984). This review will discuss one such interaction between pp60 src and host cell proteins. This interaction occurs between newly synthesized molecules of pp60 src and two cellular proteins of Mr 90 000 (pp90) and 50 000 (pp50). The kinetics and localization of this interaction suggest that the cellular pp90 and pp50 proteins are involved in some aspect of the processing of pp60 src before it reaches its residence in the plasma membrane (Courtneidge and Bishop 1982; BRUGGE et al. 1983). pp90 and pp50 have also been shown to associate with many retrovirus-encoded transforming proteins other than pp60 src (Lipsich et al. 1982; Adkins et al. 1982). This suggests that pp50 and pp90 may play a common role in the events which take place after transformation by at least one class of retrovirus transforming proteins.


Uninfected Cell Rous Sarcoma Virus Chicken Embryo Fibroblast Nonpermissive Temperature Glycerol Gradient 
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  1. Adkins B, Hunter T, Sefton BM (1982) The transforming proteins of PRCII virus and Rous sarcoma virus form a complex with the same two cellular phosphoproteins. J Virol 43: 448–455PubMedGoogle Scholar
  2. Bishop JM, Varmus H (1982) Functions and origins of retroviral transforming genes. In: Weiss R, Teich N, Varmus H, Coffin J (eds) RNA tumor viruses. Cold Spring Harbor Press, New York, pp 999–1108Google Scholar
  3. Blobel G (1982) Regulation of intracellular protein traffic. Cold Spring Harbor Symposia on quantitative biology, vol XLVI. Cold Spring Harbor Press, New York, pp 7–16Google Scholar
  4. Brugge JS, Darrow D (1982) Rous sarcoma virus-induced phosphorylation of a 50,000 molecular weight cellular protein. Nature 295: 250–253PubMedCrossRefGoogle Scholar
  5. Brugge JS, Erikson RL (1977) Identification of a transformation-specific antigen induced by an avian sarcoma virus. Nature 269: 346–348PubMedCrossRefGoogle Scholar
  6. Brugge J, Erikson E, Erikson RL (1981) The specific interaction of the Rous sarcoma virus transforming protein, pp60src, with two cellular proteins. Cell 25: 363–372PubMedCrossRefGoogle Scholar
  7. Brugge JS, Darrow D, Lipsich LA, Yonemoto Y (1982) The association of the transforming protein of Rous sarcoma virus with two cellular phosphoproteins. In: Rauuscher R (ed) Oncogenes: evaluation of basic findings and clinical potential. Liss, New York, pp 135–148Google Scholar
  8. Brugge JS, Yonemoto W, Darrow D (1983) Interaction between the Rous sarcoma virus transforming protein and two cellular phosphoproteins: Analysis of the turnover and distribution of this complex. Mol Cell Biol 3: 9–19PubMedGoogle Scholar
  9. Bryant D, Parson JT (1982) Site directed mutagenesis of the src gene of Rous sarcoma virus: construction and characterization of a deletion mutant temperature sensitive for transformation. J Virol 44: 683–691PubMedGoogle Scholar
  10. Bryant D, Parson JT (1983) Site-directed point mutation in the src gene of Rous sarcoma virus results in an inactive src gene product. J Virology 45: 1211–1216PubMedGoogle Scholar
  11. Carr SA, Biemann K, Shoji S, Parmelee DC, Titani K (1982) N-teradecanoyl is the NH2-terminal blocking group of the catalytic subunit of cyclic AMP-dependent protein kinase from bovine cardiac muscle. Proc Natl Acad Sci USA 79: 6128–6131PubMedCrossRefGoogle Scholar
  12. Cohen P (1982) The role of protein phosphorylation in neural and hormonal control of cellular activity. Nature 296: 613–620PubMedCrossRefGoogle Scholar
  13. Collett MS, Erikson RL (1978) Protein kinase activity associated with the avian sarcoma virus src gene product. Proc Natl Acad Sci USA 75: 2021–2024PubMedCrossRefGoogle Scholar
  14. Collett MS, Brugge JS, Erikson RL (1978) Characterization of a normal avian cell protein related to the avian sarcoma virus transforming gene product. Cell 15: 1363PubMedCrossRefGoogle Scholar
  15. Courtneidge SA, Bishop JM (1982) Transit of pp60v-src to the plasma membrane. Proc Natl Acad Sci USA 79: 7117–7121PubMedCrossRefGoogle Scholar
  16. Courtneidge SA, Levinson AD, Bishop JM (1980) The protein encoded by the transforming gene of avian sarcoma virus (pp60src) and homologous protein in normal cells (pp60proto-src) are associated with the plasma membrane. Proc Natl Acad Sci USA 77: 3783–3787PubMedCrossRefGoogle Scholar
  17. Cross FR, Hanafusa H (1983) Local mutagenesis of Rous sarcoma virus: the major sites of tyrosine and serine phosphorylation are dispensable for transformation. Cell 34: 597–608PubMedCrossRefGoogle Scholar
  18. Cross F, Garber E, Pellman D, Hanafusa H (1984) A N-terminal region of p60src is required for its myristylation and membrane association, and for cell transformation. Mol Cell Biol 4: 1834–1842PubMedGoogle Scholar
  19. Dougherty JJ, Puri RK, Toft DO (1984) Polypeptide components of two 8S forms chicken oviduct progesterone receptor. J Biol Chem 259: 8004–8009PubMedGoogle Scholar
  20. Erikson E, Erikson RL (1980) Identification of a cellular protein substrate phosphorylated by the avian sarcoma virus-transforming gene product. Cell 21: 829–836PubMedCrossRefGoogle Scholar
  21. Fincham V, Chiswell DJ, Wyke J (1982) Mapping of nonconditional and conditional mutants in the src gene of Prague strain Rous sarcoma virus. Virology 116: 72–83PubMedCrossRefGoogle Scholar
  22. Gilmore T, Radke K, Martin GS (1982) Tyrosine phosphorylation of a 50K cellular polypeptide associated with the Rous sarcoma virus-transforming protein, pp60src. Mol Cell Biol 2: 199–206PubMedGoogle Scholar
  23. Hanafusa H (1977) Cell transformation by RNA tumor viruses. In: Fraenkel-Conrat H, Wagner RP (eds) Comprehensive virology. Plenum, New York, pp 401–483Google Scholar
  24. Hunter T, Sefton B (1980) Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc Natl Acad Sci USA 77: 1311–1315PubMedCrossRefGoogle Scholar
  25. Iba H, Takeya T, Cross F, Hanafusa T, Hanafusa H (1984) Rous sarcoma virus variants which carry the cellular src gene instead of the viral src gene cannot transform chicken embryo fibroblasts. Proc Natl Acad Sci USA 81: 4424–4428PubMedCrossRefGoogle Scholar
  26. Johnson PJ, Coussens PM, Danko AV, Shalloway D (1985) Overexpressed pp60c-src can induce focus formation without complete transformation of NIH 3T3 cells. Mol Cell Biol 4: 454–467Google Scholar
  27. Kasambalides EJ, Lanks KW (1979) Patterns of proteins synthesized by nonproliferating murine L cells. Exp Cell Res 118: 269–275PubMedCrossRefGoogle Scholar
  28. Kawai S, Hanafusa H (1971) The effects of reciprocal changes in the temperature on the transformed state of cells infected with a Rous sarcoma virus mutant. Virology 46: 470–479PubMedCrossRefGoogle Scholar
  29. Kelley PM, Schlesinger J (1978) The effect of amino acid analogues and heat shock on gene expression in chicken embryo fibroblasts. Cell 15: 1277–1286PubMedCrossRefGoogle Scholar
  30. Krebs EG, Beavo JA (1979) Phosphorylation and dephosphorylation of enzymes. Ann Rev Biochem 48: 923–959PubMedCrossRefGoogle Scholar
  31. Krueger JK, Garber EA, Chin SS-M, Hanafusa H, Goldberg AR (1984) Size variant pp60src proteins of recovered avian sarcoma viruses interact with adhesion plaques as peripheral membrane proteins: effects on cell transformation. Mol Cell Biol 4: 454–467PubMedGoogle Scholar
  32. Lanks KW, Kasambalides EJ, Chinkers M, Brugge JS (1982) A major cytoplasmic glucose-regulated protein is associated with the Rous sarcoma virus pp60csrc protein. J Biol Chem 257: 8604–8607PubMedGoogle Scholar
  33. Lee JS, Varmus HE, Bishop JM (1979) Virus-specific messenger RNAs in permissive cells infected by avian sarcoma virus. J Biol Chem 254: 8015–8022PubMedGoogle Scholar
  34. Levinson AD, Oppermann H, Levintow L, Varmus HE, Bishop JB (1978) Evidence that the transforming gene of avian sarcoma virus encodes a protein kinase associated with a phosphoprotein. Cell 15: 561–572PubMedCrossRefGoogle Scholar
  35. Lipsich LA, Cutt J, Brugge JS (1982) Association of the transforming proteins of Rous, Fujinami and Y73 avian sarcoma viruses with the same two cellular proteins. Mol Cell Biol 2: 875–880PubMedGoogle Scholar
  36. Lipsich LA, Lewis AJ, Brugge JS (1983) Isolation of monoclonal antibodies which recognize the transforming proteins of avian sarcoma viruses. J Virol 48: 352–360PubMedGoogle Scholar
  37. Mathey-Prevot B, Shibuya M, Samarut J, Hanafusa H (1984) Revertants and partial transformants of rat fibroblasts infected with Fujinami sarcoma virus. J Virol 50: 325–334PubMedGoogle Scholar
  38. Oppermann H, Levinson W, Bishop JM (1981 a) A cellular protein that associates with a transforming protein of Rous sarcoma virus is also a heat-shock protein. Proc Natl Acad Sci USA 78: 1067–1071PubMedCrossRefGoogle Scholar
  39. Oppermann H, Levinson AD, Levintow L, Varmus HE, Bishop JM, Kawai S (1981b) Two cellular proteins that immunoprecipitate with the transforming protein of Rous sarcoma virus. Virology 113: 736–751PubMedCrossRefGoogle Scholar
  40. Parsons JD, Bryant D, Wilkerson V, Gilmartin G (1984) Site directed mutagenesis of Rous sarcoma virus: Identification of functional domains required for transformation. In: Van de Woude GF, Levine AJ, Topp WC, Watson JD (eds) Cancer cells 2: oncogenes and viral genes. Cold Spring Harbor, New York, pp 37–42Google Scholar
  41. Purchio AF, Erikson E, Brugge JS, Erikson RL (1978) Identification of a polypeptide encoded by the avian sarcoma virus src gene. Proc Natl Acad Sci USA 75: 1567–1571PubMedCrossRefGoogle Scholar
  42. Radke K, Martin GS (1979) Transformation by Rous sarcoma virus: effects of src gene expression on the synthesis and phosphorylation of cellular polypeptides. Proc Natl Acad Sci USA 76: 5213–5216CrossRefGoogle Scholar
  43. Rangel-Aldao R, Rosen OM (1976) Mechanism of self-phosphorylation of adenosine 3′:5″-monophosphate-dependent protein kinase from bovine cardiac muscle. J Biol Chem 251: 7526–7540PubMedGoogle Scholar
  44. Schlesinger MJ, Ashburner M, Tissieres A (eds) (1982) Heat shock: from bacteria to man. Cold Spring Harbor Laboratory, New YorkGoogle Scholar
  45. Schuh S, Yonemoto W, Brugge J, Bauer VJ, Riehl R, Sullivan WP, Toft DO. A 90,000 dalton binding protein common to both steroid receptors and the Rous sarcoma virus transforming protein pp60v-src. J Biol Chem 260, in pressGoogle Scholar
  46. Sefton BM, Hunter T (1984) Tyrosine protein kinases. In: Greengard P, Robison GA (eds) Advances in cyclic nucleotide and protein phosphorylation research. Raven Press, New York, pp 195–226Google Scholar
  47. Sefton BM, Walter G (1982) An antiserum specific for the carboxy terminus of the transforming protein of Rous sarcoma virus. J Virol 44: 467–474PubMedGoogle Scholar
  48. Sefton BM, Beemon K, Hunter T (1978) Comparison of the expression of the src gene of Rous sarcoma virus in vitro and in vivo. J Virol 28: 957–971PubMedGoogle Scholar
  49. Sefton BM, Hunter T, Ball EH, Singer SJ (1981) Vinculin: A cytoskeletal target of the transforming protein of Rous sarcoma virus. Cell 24: 165–174PubMedCrossRefGoogle Scholar
  50. Sefton BM, Cooper JA, Trowbridge S, Scolnick EM (1982) The transforming proteins of Rous sarcoma virus, Harvey sarcoma virus and Abelson virus contain tightly bound lipid. Cell 31: 465–474PubMedCrossRefGoogle Scholar
  51. Smart JE, Oppermann H, Czernilofsky AP, Purchio AF, Erikson RL, Bishop JM (1981) 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: 6013–6017PubMedCrossRefGoogle Scholar
  52. Sullivan WP, Vroman BT, Bauer VJ, Puri RK, Riehl RM, Pearson GR, Toft DO Isolation of a steroid receptor-binding protein from the chicken oviduct and production of monoclonal antibodies. Biochem (in press)Google Scholar
  53. Tamura T, Bauer H, Birr C, Rudiger P (1983) Antibodies against synthetic peptides as a tool for functional analysis of the transforming protein pp60src. Cell 34: 587–596PubMedCrossRefGoogle Scholar
  54. Yonemoto W, Lipsich L, Darrow D, Brugge JS (1982) An analysis of the interaction of the Rous sarcoma virus transforming protein, pp60src, with a major heat shock protein. In: Schlesinger MJ, Ashburner M, Tissieres A (eds) Heat shock proteins: from bacteria to man. Cold Spring Harbor Laboratory, New York, pp 289–298Google Scholar
  55. Walsh DA, Krebs EG (1973) Protein kinases. In: Bayer P (ed) The enzymes, vol 8. Academic, New York, p 555Google Scholar
  56. Welch WJ, Feramisco JR (1982) Purification of the major mammalian heat shock proteins. J Biol Chem 257: 14949–14959PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1986

Authors and Affiliations

  • J. S. Brugge
    • 1
  1. 1.Department of MicrobiologyState University of New York at Stony BrookStony BrookUSA

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