Fibroblasts transformed with v-src show enhanced formation of an inositol tetrakisphosphate.
The tyrosine kinase pp60v-src, encoded by the v-src oncogene, seems to regulate phosphatidylinositol metabolism. The effect of pp60v-src on control points in inositol phosphate production was examined by measuring the amounts of inositol polyphosphates in Rat-1 cells expressing wild-type or mutant forms of the protein. Expression of v-src-resulted in a five- to sevenfold elevation in the steady-state amount of an isomer of inositol tetrakisphosphate, whereas the concentrations of inositol trisphosphates or other inositol tetrakisphosphates were not affected. The activity of a key enzyme in the formation of inositol tetrakisphosphates, inositol (1,4,5)-trisphosphate 3-kinase, was increased six- to eightfold in cytosolic extracts prepared from the v-src-transformed cells, suggesting that this enzyme may be one target for the pp60v-src kinase and that it may participate in the synthesis of novel, higher order inositol phosphates.
Johnson
R M
RM
Department of Pharmacology, University of Virginia School of Medicine, Charlottesville 22908.
Wasilenko
W J
WJ
Mattingly
R R
RR
Weber
M J
MJ
Garrison
J C
JC
D000818:Animals; D002461:Cell Line, Transformed; D005347:Fibroblasts / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D007536:Isomerism; D015688:Oncogene Protein pp60(v-src); D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D012191:Retroviridae Proteins / Q000502:physiology*; D013403:Sugar Phosphates / Q000378:metabolism*
D007295:Inositol Phosphates; D012191:Retroviridae Proteins; D013403:Sugar Phosphates; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src)