Mutant but not normal p21 ras elevates inositol phospholipid breakdown in two different cell systems.

Expression of oncogenic mutant p21 ras either in stably transformed NIH3T3 fibroblasts or transiently in COS-1 cells elevates the basal rate of inositol phosphate production. Additional mutations in the effector region or the carboxy terminal region which abolish transforming capacity on NIH3T3 cells block the effect of oncogenic mutant p21 ras on basal rates. Overexpression of normal (Gly12) p21 ras has no such effect on this second messenger signalling system. These differences between overexpressed normal p21 ras and oncogenic mutant p21 ras strongly suggest that the increased basal rate of inositol phosphate production is a direct consequence of constitutively activated p21 ras activity.