Role of oligomerization of the S13 Env-Sea oncoprotein in cell transformation.
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.
Morimoto
A M
AM
Department of Microbiology, State University of New York at Stony Brook, 11794-5222.
Hayman
M J
MJ
D001355:Alpharetrovirus / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient; D006023:Glycoproteins / Q000378:metabolism; D006596:Hexosaminidases / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000276:immunology / Q000378:metabolism*; D010084:Oxidation-Reduction; D010766:Phosphorylation; D019000:Phosphotyrosine; D011233:Precipitin Tests; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism
D006023:Glycoproteins; D009856:Oncogene Proteins, Viral; C055694:env-sea oncogene protein, Avian Erythroblastosis Retrovirus; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D006596:Hexosaminidases