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)P3 3-kinase in cytosolic extracts [Johnson, Wasilenko, Mattingly, Weber and Garrison (1989) Science 246, 121-124]. This study confirms these results using another v-src-transformed Rat-1 cell line (B31 cells) and investigates the molecular mechanism by which pp60v-src activates Ins(1,4,5)P3 3-kinase. The mRNA and protein levels for two rat isoforms of Ins(1,4,5)P3 3-kinase were determined in the v-src-transformed cell line. Both the mRNA and protein levels for isoform A were elevated in v-src-transformed Rat-1 cells while those for isoform B were not significantly affected. Moreover, stable expression of either form of Ins(1,4,5)P3 3-kinase in the B31 v-src-transformed Rat-1 cell line did not result in tyrosine phosphorylation of Ins(1,4,5)P3 3-kinase A or B. These results suggest that at least one mechanism by which the v-src oncogene increases the activity of the Ins(1,4,5)P3 3-kinase in the Rat-1 transformed fibroblast is by increasing the level of expression of Ins(1,4,5)P3 3-kinase A.
Woodring
P J
PJ
Department of Pharmacology, University of Virginia School of Medicine, Charlottesville 22908, USA.
Garrison
J C
JC
D000818:Animals; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D004591:Electrophoresis, Polyacrylamide Gel; D000939:Epitopes; D005347:Fibroblasts / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D016391:Genes, src; D009842:Oligopeptides; D015688:Oncogene Protein pp60(v-src) / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014443:Tyrosine / Q000378:metabolism
D000939:Epitopes; D009842:Oligopeptides; D010455:Peptides; D012333:RNA, Messenger; D014443:Tyrosine; C085706:FLAG peptide; D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase; D015688:Oncogene Protein pp60(v-src)