Serum-stimulated phosphatidylinositol turnover is enhanced in 3T3 cells with active pp60v-src.
Interaction between the viral oncoprotein pp60v-src and the phosphatidylinositol (PI) pathway was studied in a Balb/c 3T3 cell line expressing a temperature-sensitive pp60v-src (LA90). The rate of PI turnover was estimated from the accumulation of water soluble inositol phosphates in the presence of Li+. Though the basal rate of inositol phosphate accumulation was not altered by activation of pp60v-src, the rate of accumulation after stimulation with serum was twice as great in cells with active v-src protein (permissive temperature, 35 degrees C) as in cells at the restrictive temperature (40 degrees C). This difference was not due to the change in temperature, because serum-stimulated control Balb/c 3T3 cells accumulated the same amounts of inositol phosphates at 35 degrees and 40 degrees C. The pp60v-src effect required the viral kinase to be active for 8-24 h and could be blocked by the protein synthesis inhibitor cycloheximide. Long term activation of other tyrosine protein kinases, such as the EGF receptor, did not induce this effect. Moreover, stimulation of PI turnover in LA90 cells by PDGF and thrombin was not enhanced at 35 degrees C, suggesting that the effect of pp60v-src is not general to all receptor systems coupled to the PI pathway, but is specific to an unknown component of serum. The effect was not due to increased phosphoinositide levels in cells with active pp60v-src. Finally, it did not correlate with any increase in serum-induced mitogenicity.
Gray
G M
GM
Division of Toxicology, University of Rochester Medical Center, New York 14642.
Macara
I G
IG
D000818:Animals; D001790:Blood Physiological Phenomena; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D004789:Enzyme Activation; D006133:Growth Substances / Q000494:pharmacology; D051379:Mice; D015688:Oncogene Protein pp60(v-src) / Q000502:physiology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D013696:Temperature
D006133:Growth Substances; D010716:Phosphatidylinositols; D004247:DNA; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src)