Evidence that the transforming gene of avian sarcoma virus encodes a protein kinase associated with a phosphoprotein
- PMID: 214242
- DOI: 10.1016/0092-8674(78)90024-7
Evidence that the transforming gene of avian sarcoma virus encodes a protein kinase associated with a phosphoprotein
Abstract
Avian sarcoma virus (ASV) induces sarcomas in animals and transforms fibroblasts to a neoplastic state in cell culture. A single viral gene (src) is responsible for both the induction and maintenance of neoplastic transformation. Recent work has identified a protein with a molecular weight of 60,000 daltons that is apparently encoded in src and may be the effector molecule for the gene (Brugge and Erikson, 1977; Purchio et al, 1978). The putative product of src can be immunoprecipitated by antisera obtained from rabbits bearing tumors induced by ASV. We have used this approach to isolate the protein to characterize further its genetic origins and possible function. Our rabbit tumor antisera precipitated a protein with a molecular weight of 60,000 daltons; according to serological, biochemical and genetic criteria, this protein is encoded in src. We found that this protein is phosphorylated and therefore denoted it pp60. Phosphorylation of pp60 could be accomplished in vitro with extracts of ASV-infected cells. A temperature-sensitive conditional mutation in src had no demonstrable effect on either the production or stability of pp60 in the infected cell, but phosphorylation of the protein was temperature-sensitive. Since the mutant src is not expressed at the restrictive temperature, our findings raise the possibility that phosphorylation of pp60 is required for its function as the putative effector of src. Immunoprecipitates prepared with extracts of ASV-infected cells and the rabbit tumor antisera contained a protein kinase activity that catalyzed phosphorylation of the heavy chains of immunoglobulin molecules, using either ATP or GTP as phosphate donor. The kinase activity immunoprecipitated in parallel with pp60 was obtained only from cells that contained a functioning product of src and could not be precipitated with antisera directed against structural proteins of ASV. A temperature-sensitive conditional mutation in src caused the kinase activity to be thermally inactivated in vitro far more rapidly than the activity from cells infected with wild-type virus. We conclude that both the protein kinase and pp60 are encoded in src, and that the enzymatic activity may be an intrinsic property of pp60. Phosphorylation of pp60 in cellular extracts was inhibited by calcium ion, whereas the immunoprecipitable kinase activity was not, suggesting that the kinase responsible for pp60 phosphorylation may be distinct from that encoded in src. Collett and Erikson (1978) have also identified a protein kinase activity associated with pp60. These findings raise the possibility that phosphorylation of specific cellular targets might account for transformation of the host cell by src.
Similar articles
-
Protein kinase activity associated with the avian sarcoma virus src gene product.Proc Natl Acad Sci U S A. 1978 Apr;75(4):2021-4. doi: 10.1073/pnas.75.4.2021. Proc Natl Acad Sci U S A. 1978. PMID: 205879 Free PMC article.
-
Detection of the viral sarcoma gene product in cells infected with various strains of avian sarcoma virus and of a related protein in uninfected chicken cells.J Virol. 1979 Mar;29(3):1196-203. doi: 10.1128/JVI.29.3.1196-1203.1979. J Virol. 1979. PMID: 221673 Free PMC article.
-
Src Gene product from different strains of avian sarcoma virus: Kinetics and possible mechanism of heat inactivation of protein kinase activity from cells infected by transformation-defective, temperature-sensitive mutant and wild-type virus.Proc Natl Acad Sci U S A. 1979 Feb;76(2):967-71. doi: 10.1073/pnas.76.2.967. Proc Natl Acad Sci U S A. 1979. PMID: 218225 Free PMC article.
-
The transforming protein of avian sarcoma viruses and its homologue in normal cells.Curr Top Microbiol Immunol. 1981;91:25-40. doi: 10.1007/978-3-642-68058-8_2. Curr Top Microbiol Immunol. 1981. PMID: 6273069 Review. No abstract available.
-
Molecular events in cells transformed by Rous Sarcoma virus.J Cell Biol. 1980 Nov;87(2 Pt 1):319-25. doi: 10.1083/jcb.87.2.319. J Cell Biol. 1980. PMID: 6253501 Free PMC article. Review.
Cited by
-
A Fluorescence-Based Sensor for Calibrated Measurement of Protein Kinase Stability in Live Cells.bioRxiv [Preprint]. 2023 Dec 8:2023.12.07.570636. doi: 10.1101/2023.12.07.570636. bioRxiv. 2023. Update in: Protein Sci. 2024 Jun;33(6):e5023. doi: 10.1002/pro.5023 PMID: 38106090 Free PMC article. Updated. Preprint.
-
Rous sarcoma virus mutant dlPA105 induces different transformed phenotypes in quail embryonic fibroblasts and neuroretina cells.J Virol. 1987 Aug;61(8):2530-9. doi: 10.1128/JVI.61.8.2530-2539.1987. J Virol. 1987. PMID: 3037115 Free PMC article.
-
Product of in vitro translation of the Rous sarcoma virus src gene has protein kinase activity.J Virol. 1979 Apr;30(1):311-8. doi: 10.1128/JVI.30.1.311-318.1979. J Virol. 1979. PMID: 225522 Free PMC article.
-
Enhanced phosphorylation of many endogenous protein substrates in human fibroblasts transformed by simian virus 40.Proc Natl Acad Sci U S A. 1979 Dec;76(12):6396-400. doi: 10.1073/pnas.76.12.6396. Proc Natl Acad Sci U S A. 1979. PMID: 230507 Free PMC article.
-
Immune response to the src gene product in mice bearing tumors induced by injection of avian sarcoma virus-transformed mouse cells.J Virol. 1979 Oct;32(1):40-6. doi: 10.1128/JVI.32.1.40-46.1979. J Virol. 1979. PMID: 232185 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Miscellaneous