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. 1994 Mar;68(3):1837–1842. doi: 10.1128/jvi.68.3.1837-1842.1994

Role of oligomerization of the S13 Env-Sea oncoprotein in cell transformation.

A M Morimoto 1, M J Hayman 1
PMCID: PMC236646  PMID: 7509003

Abstract

The env-sea oncogene is a fusion of the S13 viral envelope gene, env, and cell-derived sequences encoding a tyrosine kinase domain, termed sea. The Env-Sea oncoprotein is synthesized as a precursor of 155 kDa which undergoes proteolytic processing to generate a disulfide-linked complex of the proteins gp85 and gp70. We analyzed the oligomeric state of the Env-Sea oncoprotein in S13-transformed cells and demonstrate that both gp155 and the gp85-gp70 complex can oligomerize. To address the relevance of these oligomers in transformation by S13, a mutant that is temperature sensitive for the transformed phenotype was used. The tyrosine-phosphorylated oligomers of gp155 were found at the nonpermissive temperature, and thus oligomerization per se appears to be insufficient to elicit a transformed phenotype. Efficient intracellular transport of gp155 appears to be required to generate a tyrosine-phosphorylated oligomer of the gp85-gp70 complex, the presence of which correlates with the transformed phenotype. This gp85-gp70 complex appeared to have a higher level of kinase activity than the other forms of the Env-Sea protein. These results suggest that oligomerization, transport, and intracellular localization represent levels at which the oncogenic activity of the Env-Sea oncoprotein may be regulated.

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Selected References

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

  1. Bargmann C. I., Hung M. C., Weinberg R. A. Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p185. Cell. 1986 Jun 6;45(5):649–657. doi: 10.1016/0092-8674(86)90779-8. [DOI] [PubMed] [Google Scholar]
  2. Bargmann C. I., Weinberg R. A. Oncogenic activation of the neu-encoded receptor protein by point mutation and deletion. EMBO J. 1988 Jul;7(7):2043–2052. doi: 10.1002/j.1460-2075.1988.tb03044.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bertics P. J., Gill G. N. Self-phosphorylation enhances the protein-tyrosine kinase activity of the epidermal growth factor receptor. J Biol Chem. 1985 Nov 25;260(27):14642–14647. [PubMed] [Google Scholar]
  4. Beug H., Hayman M. J., Graf T., Benedict S. H., Wallbank A. M., Vogt P. K. S13, a rapidly oncogenic replication-defective avian retrovirus. Virology. 1985 Aug;145(1):141–153. doi: 10.1016/0042-6822(85)90209-0. [DOI] [PubMed] [Google Scholar]
  5. Beug H., Hayman M. J. Temperature-sensitive mutants of avian erythroblastosis virus: surface expression of the erbB product correlates with transformation. Cell. 1984 Apr;36(4):963–972. doi: 10.1016/0092-8674(84)90046-1. [DOI] [PubMed] [Google Scholar]
  6. Böni-Schnetzler M., Pilch P. F. Mechanism of epidermal growth factor receptor autophosphorylation and high-affinity binding. Proc Natl Acad Sci U S A. 1987 Nov;84(22):7832–7836. doi: 10.1073/pnas.84.22.7832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Crowe A. J., Hayman M. J. Altered glycosylation of the env-sea oncoprotein inhibits intracellular transport and transformation. Cell Growth Differ. 1993 May;4(5):403–410. [PubMed] [Google Scholar]
  8. Crowe A. J., Hayman M. J. Post-translational modifications of the env-sea oncogene product: the role of proteolytic processing in transformation. Oncogene. 1993 Jan;8(1):181–189. [PubMed] [Google Scholar]
  9. Downward J., Yarden Y., Mayes E., Scrace G., Totty N., Stockwell P., Ullrich A., Schlessinger J., Waterfield M. D. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature. 1984 Feb 9;307(5951):521–527. doi: 10.1038/307521a0. [DOI] [PubMed] [Google Scholar]
  10. Einfeld D., Hunter E. Oligomeric structure of a prototype retrovirus glycoprotein. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8688–8692. doi: 10.1073/pnas.85.22.8688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Giordano S., Ponzetto C., Di Renzo M. F., Cooper C. S., Comoglio P. M. Tyrosine kinase receptor indistinguishable from the c-met protein. Nature. 1989 May 11;339(6220):155–156. doi: 10.1038/339155a0. [DOI] [PubMed] [Google Scholar]
  12. Hammacher A., Mellström K., Heldin C. H., Westermark B. Isoform-specific induction of actin reorganization by platelet-derived growth factor suggests that the functionally active receptor is a dimer. EMBO J. 1989 Sep;8(9):2489–2495. doi: 10.1002/j.1460-2075.1989.tb08385.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Huff J. L., Jelinek M. A., Borgman C. A., Lansing T. J., Parsons J. T. The protooncogene c-sea encodes a transmembrane protein-tyrosine kinase related to the Met/hepatocyte growth factor/scatter factor receptor. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6140–6144. doi: 10.1073/pnas.90.13.6140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jia R., Mayer B. J., Hanafusa T., Hanafusa H. A novel oncogene, v-ryk, encoding a truncated receptor tyrosine kinase is transduced into the RPL30 virus without loss of viral sequences. J Virol. 1992 Oct;66(10):5975–5987. doi: 10.1128/jvi.66.10.5975-5987.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Knight J., Smith D. R., Hayman M. J. Identification of two additional v-sea-encoded proteins in avian erythroblastosis virus, S13-infected fibroblasts. Virology. 1990 Sep;178(1):232–237. doi: 10.1016/0042-6822(90)90398-b. [DOI] [PubMed] [Google Scholar]
  16. Knight J., Zenke M., Disela C., Kowenz E., Vogt P., Engel J. D., Hayman M. J., Beug H. Temperature-sensitive v-sea transformed erythroblasts: a model system to study gene expression during erythroid differentiation. Genes Dev. 1988 Feb;2(2):247–258. doi: 10.1101/gad.2.2.247. [DOI] [PubMed] [Google Scholar]
  17. Pelley R. J., Maihle N. J., Boerkoel C., Shu H. K., Carter T. H., Moscovici C., Kung H. J. Disease tropism of c-erbB: effects of carboxyl-terminal tyrosine and internal mutations on tissue-specific transformation. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7164–7168. doi: 10.1073/pnas.86.18.7164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Perez L. G., Davis G. L., Hunter E. Mutants of the Rous sarcoma virus envelope glycoprotein that lack the transmembrane anchor and cytoplasmic domains: analysis of intracellular transport and assembly into virions. J Virol. 1987 Oct;61(10):2981–2988. doi: 10.1128/jvi.61.10.2981-2988.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Perez L. G., Hunter E. Mutations within the proteolytic cleavage site of the Rous sarcoma virus glycoprotein that block processing to gp85 and gp37. J Virol. 1987 May;61(5):1609–1614. doi: 10.1128/jvi.61.5.1609-1614.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rosen O. M., Herrera R., Olowe Y., Petruzzelli L. M., Cobb M. H. Phosphorylation activates the insulin receptor tyrosine protein kinase. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3237–3240. doi: 10.1073/pnas.80.11.3237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schlessinger J. Signal transduction by allosteric receptor oligomerization. Trends Biochem Sci. 1988 Nov;13(11):443–447. doi: 10.1016/0968-0004(88)90219-8. [DOI] [PubMed] [Google Scholar]
  22. Sherr C. J., Rettenmier C. W., Sacca R., Roussel M. F., Look A. T., Stanley E. R. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell. 1985 Jul;41(3):665–676. doi: 10.1016/s0092-8674(85)80047-7. [DOI] [PubMed] [Google Scholar]
  23. Smith D. R., Vogt P. K., Hayman M. J. The v-sea oncogene of avian erythroblastosis retrovirus S13: another member of the protein-tyrosine kinase gene family. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5291–5295. doi: 10.1073/pnas.86.14.5291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Willey R. L., Klimkait T., Frucht D. M., Bonifacino J. S., Martin M. A. Mutations within the human immunodeficiency virus type 1 gp160 envelope glycoprotein alter its intracellular transport and processing. Virology. 1991 Sep;184(1):319–329. doi: 10.1016/0042-6822(91)90848-6. [DOI] [PubMed] [Google Scholar]
  25. Wills J. W., Srinivas R. V., Hunter E. Mutations of the Rous sarcoma virus env gene that affect the transport and subcellular location of the glycoprotein products. J Cell Biol. 1984 Dec;99(6):2011–2023. doi: 10.1083/jcb.99.6.2011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Yarden Y., Ullrich A. Growth factor receptor tyrosine kinases. Annu Rev Biochem. 1988;57:443–478. doi: 10.1146/annurev.bi.57.070188.002303. [DOI] [PubMed] [Google Scholar]

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