| Gene information | Literature | Expression | lncRNA | Mutation | Homolog |
Basic Information | |
|---|---|
Gene ID | 30816 |
Name | ERVW-1 |
Synonymous | endogenous retrovirus group W, member 1;ERVW-1;endogenous retrovirus group W, member 1 |
Definition | HERV-7q envelope protein|HERV-W Env glycoprotein|HERV-W envelope protein|HERV-W_7q21.2 provirus ancestral Env polyprotein|HERV-W{7q21.1} provirus ancestral Env polyprotein|HERV-tryptophan envelope protein|endogenous retroviral family W, env(C7), member 1| |
Position | 7q21.2 |
Gene type | protein-coding |
Title | Abstract |
| The tyrosines in the bidentate motif of the env-sea oncoprotein are essential for cell transformation and are binding sites for Grb2 and the tyrosine phosphatase SHP-2. | The transforming gene product of the S13 avian erythroblastosis virus, the env-sea protein, is a member of the hepatocyte growth factor receptor family of tyrosine kinases comprising Met, Ron, and Sea. Like ALL three members of this family, the env-sea protein has a so-called bidentate motif (Y557INMAVTY564VNL) composed of two tandemly arranged tyrosines in the carboxyl terminus. To investigate whether the tyrosine residues in this motif are essential for the env-sea-mediated transformation, we generated tyrosine to phenylalanine mutations. Substitutions of both tyrosine residues resulted in complete loss of the transforming activity. In contrast, single mutations at either tyrosine did not inhibit transformation of Rat1 cells, and mutation of tyrosine 564 actually increased transformation of Rat 1 cells. To define signaling pathways activated by the env-sea protein, we looked for protein-protein interactions mediated by these tyrosine residues. We show that the bidentate motif is responsible for interaction with the adapter protein Grb2, phosphatidylinositol 3-kinase, and the tyrosine phosphatase SHP-2. Furthermore, we show that microinjected Src homology 2 domains from either Grb2 or SHP-2 blocked the transforming activity of the env-sea protein. Together, these results suggest that the tyrosines within the bidentate motif are essential for the env-sea transformation. |
| Altered glycosylation of the env-sea oncoprotein inhibits intracellular transport and transformation. | The transforming gene product of the S13 avian erythroblastosis virus, env-sea, is a member of the growth factor receptor class of tyrosine kinases. The env-sea precursor protein gp155env-sea is proteolytically processed into the mature cleavage products gp85env and gp70env-sea, which are subsequently terminally glycosylated and transported to the cell surface. Previous studies have shown that the abnormal glycosylation of gp155env-sea induced by the carbohydrate processing inhibitor castanospermine blocks the proteolytic cleavage of gp155env-sea and impairs its transforming ability. We have shown recently that an uncleaved but fully glycosylated sea-encoded protein retains the ability to transform chicken embryo fibroblasts, indicating that proteolytic processing is not essential for transformation by the env-sea tyrosine kinase. To address the question of how castanospermine blocks transformation by env-sea, differential sucrose gradient centrifugation was performed on env-sea-transformed cells treated with the inhibitor. This report shows that no surface forms of env-sea could be detected in inhibitor-treated cells, suggesting that castanospermine acts by blocking the transport of sea-encoded proteins to the cell surface. |