Transforming protein of avian sarcoma virus UR2 is associated with phosphatidylinositol kinase activity: possible role in tumorigenesis.
The transforming protein of avian sarcoma virus UR2, p68v-ros, has an associated tyrosine-specific protein kinase activity similar to that of p60v-src and several other oncogene products. However, this activity has not been linked unequivocally to transformation, and the physiological action of these proteins remains in doubt. We now have found that immunoprecipitated p68v-ros also is associated with phosphatidylinositol (PtdIns) kinase (ATP:PtdIns 4-phosphotransferase, EC 2.7.1.67) activity. PtdIns 4,5-bisphosphate [PtdIns(4,5)P2] specifically inhibits both this activity and the autophosphorylation of p68v-ros. Moreover, cells transformed by UR2 showed significant increases in 32P-labeling of PtdIns 4-phosphate (PtdIns4P) and PtdIns(4,5)P2 and in the formation of their catabolites, inositol 1,4-bisphosphate and inositol 1,4,5-trisphosphate, as compared to uninfected cells. These results suggest that a physiologically relevant function of oncogene kinases might be the phosphorylation of PtdIns and that increased turnover of PtdIns4P and PtdIns(4,5)P2 might play a role in transformation by increasing the formation of diacylglycerol, a catabolite of polyphosphoinositides that activates kinase C. This protein copurifies with the phorbol ester receptor, and its activation is likely to be intimately linked with mitogenesis. This hypothesis suggests a mechanism whereby certain oncogene proteins might cause the unrestricted growth typical of transformed cells and could explain why tumor promoters mimic many of the effects of transformation.
D019870:1-Phosphatidylinositol 4-Kinase; D001358:Avian Sarcoma Viruses / Q000201:enzymology*; D002472:Cell Transformation, Viral; D007700:Kinetics; D010716:Phosphatidylinositols / Q000378:metabolism*; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism*
D010716:Phosphatidylinositols; D010770:Phosphotransferases; D019870:1-Phosphatidylinositol 4-Kinase