TRANSFORMATION OF RAT-1 FIBROBLASTS WITH THE V-SRC ONCOGENE INDUCES INOSITOL 1,4,5-TRISPHOSPHATE 3-KINASE EXPRESSION

Transformation of Rat-1 fibroblasts with the v-src oncogene leads to a 6- to 8-fold enhancement of the activity of the Ins(1,4,5)P-3 3-kinas e in cytosolic extracts [Johnson, Wasilenko, Mattingly, Weber and Garr ison (1989) Science 246, 121-124]. This study confirms these results u sing another v-src-transformed Rat-1 cell line (B31 cells) and investi gates the molecular mechanism by which pp60(v-src) activates Ins(1,4,5 )P-3 3-kinase. The mRNA and protein levels for two rat isoforms of Ins (1,4,5)P-3 3-kinase were determined in the v-slc-transformed cell line . Both the mRNA and protein levels for isoform A were elevated in v-sr c-transformed Rat-1 cells while those for isoform B were not significa ntly affected. Moreover, stable expression of either form of Ins(1,4,5 )P-3 3-kinase in the B31 v-src-transformed Rat-1 cell line did not res ult in tyrosine phosphorylation of Ins(1,4,5)P-3 3-kinase A or B. Thes e results suggest that at least one mechanism by which the v-ac oncoge ne increases the activity of the Ins(1,4,5)P-3 3-kinase in the Rat-1 t ransformed fibroblast is by increasing the level of expression of Ins( 1,4,5)P-3 3-kinase A.