At. Glazier et al., ATTENUATION OF LPA-MEDIATED CALCIUM SIGNALING AND INOSITOL POLYPHOSPHATE PRODUCTION IN RAT-1 FIBROBLASTS TRANSFORMED BY THE V-SRC ONCOGENE, Biochemical and biophysical research communications, 245(2), 1998, pp. 607-612
Alterations in cellular signaling underlie the trans forming actions o
f many oncogenes. The vsrc oncogene tyrosine kinase, pp60(vsrc), is kn
own to alter multiple signal transduction pathways, including those in
volving phosphatidylinositol (PI) metabolism. In this study, we invest
igated the effects of vsrc-transforrmation on lysophosphatidic acid (L
PA) receptor coupling to intracellular free calcium [Ca2+](i) and PI t
urnover in rat-1 fibroblasts. In normal rat-1 cells, LPA rapidly eleva
ted [Ca2-](i) (EC50 = 10nM). In contrast, the ability of LPA to mobili
ze calcium was markedly attenuated in rat-1-vsrc cells. Further study
revealed that the LPA-mediated generation of inositol (1,4,5)P-3 and o
ther inositol polyphosphates was also markedly attenuated in the vsrc-
transformed cells. Although LPA caused a transient reduction in the le
vel of PI(4,5)P-2 in normal rat-1 cells, the agonist elevated the leve
l of PI(4,5)P-2 in the vsrc-transformed cells. These findings demonstr
ate that vsrc-transformation alters the coupling of LPA receptors to P
I turnover and calcium signaling in rat-1 cells, and point to G protei
n-coupled receptor systems as targets for modulation by the vsrc kinas
e, (C) 1998 Academic Press.