INHIBITION OF SERUM-STIMULATED AND RAS-STIMULATED DNA-SYNTHESIS BY ANTIBODIES TO PHOSPHOLIPASE-C

被引:145
作者
SMITH, MR
LIU, YL
KIM, H
RHEE, SG
KUNG, HF
机构
[1] NHLBI,BIOCHEM LAB,BETHESDA,MD 20892
[2] NCI,FREDERICK CANC RES FACIL,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701
关键词
D O I
10.1126/science.2408147
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Several immunologically distinct isozymes of inositol phospholipid-specific phospholipase C (PLC) have been purified from bovine brain. Murine NIH 3T3 fibroblasts were found to express PLC-γ, but the expression of PLC-β was barely detectable by radioimmunoassay or protein immunoblot. A mixture of monoclonal antibodies was identified that neutralizes the biological activity of both endogenous and injected purified PLC-γ. When co-injected with oncogenic Ras protein or PLC-γ, this mixture of antibodies inhibited the induction of DNA synthesis that characteristically results from the injection of these proteins into quiescent 3T3 cells. However, when oncogenic Ras protein or PLC-γ was co-injected with a neutralizing monoclonal antibody to Ras, only the DNA synthesis induced by the Ras protein was inhibited - that induced by PLC was unaffected. These results suggest that the Ras protein is an upstream effector of PLC activity in phosphoinositide-specific signal transduction and that PLC-γ activity is necessary for Ras-mediated induction of DNA synthesis.
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页码:1074 / 1077
页数:4
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