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

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 gp7O. We analyzed the oligomeric state of the Env-Sea oncoprotein in S13-transformed cells and demonstrate that both gp155 and the gp85-gp7O 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-gp7O complex, the presence of which correlates with the transformed phenotype. This gp85-gp7O 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.

Scaffolding protein Gab2 mediates fibroblast transformation by the SEA tyrosine kinase

“…The V-Sea oncogene of the avian retrovirus S13 is one such oncogene and it is derived from a cellular protein tyrosine kinase, C-SEA, whose extracellular and transmembrane domains have 'been replaced by viral envelope sequences (Smith et al, 1989). Previous studies showed that the V-SEA tyrosine kinase activity is necessary for transformation by the V-SEA protein and that cell surface localization, oligomerization by viral envelope domains and autophosphorylation are all necessary for the transforming activity of the V-SEA protein (Crowe and Hayman, 1991;Crowe and Hayman, 1993a, b;Morimoto and Hayman, 1994).…”