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. 1981 Jul;39(1):246–254. doi: 10.1128/jvi.39.1.246-254.1981

Transformation-defective mutants of Snyder-Theilen feline sarcoma virus lack tyrosine-specific protein kinase activity.

M Barbacid, L Donner, S K Ruscetti, C J Sherr
PMCID: PMC171283  PMID: 6168771

Abstract

Four phenotypically normal mink cell clones, each containing a transformation-defective provirus of the Snyder-Theilen strain of feline sarcoma virus (ST-FeSV), synthesized an 85,000-dalton viral polyprotein (P85) indistinguishable in size and antigenic complexity from that encoded by wild-type transforming ST-FeSV. An additional transformation-defective, ST-FeSV-containing flat cell clone produced a polyprotein of 88,000 daltons (P88). The viral polyproteins immunoprecipitated from cytoplasmic extracts of these cells lacked the tyrosine-specific protein kinase activity associated with the wild-type ST-FeSV gene product. In addition, the products encoded by representative transformation-defective ST-FeSV genomes were poorly phosphorylated in vivo and lacked detectable phosphotyrosine residues. Whereas proteins of ST-FeSV transformants contained elevated levels of phosphotyrosine, those of mink cells containing transformation-defective ST-FeSV exhibited phosphotyrosine levels no higher than those found in uninfected cells. These findings provide genetic evidence that the tyrosine-specific protein kinase activity associated with ST-FeSV P85 is required for virus-induced transformation.

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Selected References

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

  1. Barbacid M., Beemon K., Devare S. G. Origin and functional properties of the major gene product of the Snyder-Theilen strain of feline sarcoma virus. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5158–5162. doi: 10.1073/pnas.77.9.5158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barbacid M. Cellular transformation by subgenomic feline sarcoma virus DNA. J Virol. 1981 Jan;37(1):518–523. doi: 10.1128/jvi.37.1.518-523.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barbacid M., Lauver A. V., Devare S. G. Biochemical and immunological characterization of polyproteins coded for by the McDonough, Gardner-Arnstein, and Snyder-Theilen strains of feline sarcoma virus. J Virol. 1980 Jan;33(1):196–207. doi: 10.1128/jvi.33.1.196-207.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bensinger W. I., Robbins K. C., Greenberger J. S., Aaronson S. A. Different mechanisms for morphologic reversion of a clonal population of murine sarcoma virus-transformed nonproducer cells. Virology. 1977 Apr;77(2):750–761. doi: 10.1016/0042-6822(77)90496-2. [DOI] [PubMed] [Google Scholar]
  5. Bonner W. M., Laskey R. A. A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem. 1974 Jul 1;46(1):83–88. doi: 10.1111/j.1432-1033.1974.tb03599.x. [DOI] [PubMed] [Google Scholar]
  6. Collett M. S., Erikson R. L. Protein kinase activity associated with the avian sarcoma virus src gene product. Proc Natl Acad Sci U S A. 1978 Apr;75(4):2021–2024. doi: 10.1073/pnas.75.4.2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Donner L., Turek L. P., Ruscetti S. K., Fedele L. A., Sherr C. J. Transformation-defective mutants of feline sarcoma virus which express a product of the viral src gene. J Virol. 1980 Jul;35(1):129–140. doi: 10.1128/jvi.35.1.129-140.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Erikson E., Erikson R. L. Identification of a cellular protein substrate phosphorylated by the avian sarcoma virus-transforming gene product. Cell. 1980 Oct;21(3):829–836. doi: 10.1016/0092-8674(80)90446-8. [DOI] [PubMed] [Google Scholar]
  9. Feldman R. A., Hanafusa T., Hanafusa H. Characterization of protein kinase activity associated with the transforming gene product of Fujinami sarcoma virus. Cell. 1980 Dec;22(3):757–765. doi: 10.1016/0092-8674(80)90552-8. [DOI] [PubMed] [Google Scholar]
  10. Greenberger J. S., Anderson G. R., Aaronson S. A. Transformation-defective virus mutants in a class of morphologic revertants of sarcoma virus transformed nonproducer cells. Cell. 1974 Aug;2(4):279–286. doi: 10.1016/0092-8674(74)90022-1. [DOI] [PubMed] [Google Scholar]
  11. Hunter T., Sefton B. M. Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1311–1315. doi: 10.1073/pnas.77.3.1311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Khan A. S., Stephenson J. R. Feline leukemia virus: biochemical and immunological characterization of gag gene-coded structural proteins. J Virol. 1977 Sep;23(3):599–607. doi: 10.1128/jvi.23.3.599-607.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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. 1978 Oct;15(2):561–572. doi: 10.1016/0092-8674(78)90024-7. [DOI] [PubMed] [Google Scholar]
  14. Neil J. C., Ghysdael J., Vogt P. K. Tyrosine-specific protein kinase activity associated with p105 of avian sarcoma virus PRCII. Virology. 1981 Feb;109(1):223–228. doi: 10.1016/0042-6822(81)90493-1. [DOI] [PubMed] [Google Scholar]
  15. Oppermann H., Levinson A. D., Varmus H. E. The structure and protein kinase activity of proteins encoded by nonconditional mutants and back mutants in the sec gene of avian sarcoma virus. Virology. 1981 Jan 15;108(1):47–70. doi: 10.1016/0042-6822(81)90526-2. [DOI] [PubMed] [Google Scholar]
  16. Pawson T., Guyden J., Kung T. H., Radke K., Gilmore T., Martin G. S. A strain of Fujinami sarcoma virus which is temperature-sensitive in protein phosphorylation and cellular transformation. Cell. 1980 Dec;22(3):767–775. doi: 10.1016/0092-8674(80)90553-x. [DOI] [PubMed] [Google Scholar]
  17. Porzig K. J., Barbacid M., Aaronson S. A. Biological properties and translational products of three independent isolates of feline sarcoma virus. Virology. 1979 Jan 15;92(1):91–107. doi: 10.1016/0042-6822(79)90217-4. [DOI] [PubMed] [Google Scholar]
  18. Porzig K. J., Robbins K. C., Aaronson S. A. Cellular regulation of mammalian sarcoma virus expression: a gene regulation model for oncogenesis. Cell. 1979 Apr;16(4):875–884. doi: 10.1016/0092-8674(79)90102-8. [DOI] [PubMed] [Google Scholar]
  19. Radke K., Gilmore T., Martin G. S. Transformation by Rous sarcoma virus: a cellular substrate for transformation-specific protein phosphorylation contains phosphotyrosine. Cell. 1980 Oct;21(3):821–828. doi: 10.1016/0092-8674(80)90445-6. [DOI] [PubMed] [Google Scholar]
  20. Reynolds F. H., Jr, Van de Ven W. J., Stephenson J. R. Abelson murine leukemia virus transformation-defective mutants with impaired P120-associated protein kinase activity. J Virol. 1980 Nov;36(2):374–386. doi: 10.1128/jvi.36.2.374-386.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ruscetti S. K., Turek L. P., Sherr C. J. Three independent isolates of feline sarcoma virus code for three distinct gag-x polyproteins. J Virol. 1980 Jul;35(1):259–264. doi: 10.1128/jvi.35.1.259-264.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sefton B. M., Hunter T., Beemon K., Eckhart W. Evidence that the phosphorylation of tyrosine is essential for cellular transformation by Rous sarcoma virus. Cell. 1980 Jul;20(3):807–816. doi: 10.1016/0092-8674(80)90327-x. [DOI] [PubMed] [Google Scholar]
  23. Sefton B. M., Hunter T., Raschke W. C. Evidence that the Abelson virus protein functions in vivo as a protein kinase that phosphorylates tyrosine. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1552–1556. doi: 10.1073/pnas.78.3.1552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sherr C. J., Sen A., Todaro G. J., Sliski A., Essex M. Pseudotypes of feline sarcoma virus contain an 85,000-dalton protein with feline oncornavirus-associated cell membrane antigen (FOCMA) activity. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1505–1509. doi: 10.1073/pnas.75.3.1505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Van de Ven W. J., Reynolds F. H., Jr, Stephenson J. R. The nonstructural components of polyproteins encoded by replication-defective mammalian transforming retroviruses are phosphorylated and have associated protein kinase activity. Virology. 1980 Feb;101(1):185–197. doi: 10.1016/0042-6822(80)90495-x. [DOI] [PubMed] [Google Scholar]
  26. Wei E., Sigel S., Loh H., Way E. L. Thyrotrophin-releasing hormone and shaking behaviour in rat. Nature. 1975 Feb 27;253(5494):739–740. doi: 10.1038/253739a0. [DOI] [PubMed] [Google Scholar]
  27. Witte O. N., Dasgupta A., Baltimore D. Abelson murine leukaemia virus protein is phosphorylated in vitro to form phosphotyrosine. Nature. 1980 Feb 28;283(5750):826–831. doi: 10.1038/283826a0. [DOI] [PubMed] [Google Scholar]
  28. Witte O. N., Goff S., Rosenberg N., Baltimore D. A transformation-defective mutant of Abelson murine leukemia virus lacks protein kinase activity. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4993–4997. doi: 10.1073/pnas.77.8.4993. [DOI] [PMC free article] [PubMed] [Google Scholar]

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