Modulatory effect of the transmembrane domain of the protein-tyrosine kinase encoded by oncogene ros: biological function and substrate interaction.

摘要: Abstract There is a 3-aa insertion in the transmembrane (TM) domain of p68gag-ros protein-tyrosine kinase encoded by avian sarcoma virus UR2 v-ros as compared with that protooncogene c-ros. The effect this on biological function and biochemical properties v-Ros protein was investigated deleting these 3 aa to generate mutant TM1. This has greatly reduced transforming, mitogenic, tumorigenic activities despite fact activity cell-surface localization TM1 are unaffected. However, unlike protein, becomes glycosylated, differentially phosphorylated, fails induce tyrosine phosphorylation 88-kDa major substrate insulin receptor, receptor 1. unable associate phosphatidylinositol 3-kinase promote association 1 3-kinase. By contrast, Shc phospholipase C gamma well interaction Grb2 SOS signaling components unaltered infected cells. Our results show TM-domain sequence profoundly affects its interaction. defines pathway including 3-kinase, 1, possibly an does not overlap Ras important for full transforming mitogenic potency kinase.