RHO-FAMILY GTPASES BIND TO PHOSPHOINOSITIDE KINASES

被引:407
作者
TOLIAS, KF
CANTLEY, LC
CARPENTER, CL
机构
[1] HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115
[2] HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115
[3] BETH ISRAEL HOSP,DIV SIGNAL TRANSDUCT,BOSTON,MA 02115
关键词
D O I
10.1074/jbc.270.30.17656
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Rho family GTPases appear to play an important role in the regulation of the actin cytoskeleton, but the mechanism of regulation is unknown. Since phosphoinositide 3-kinase and phosphatidylinositol 4,5-bisphosphate have also been implicated in actin reorganization, we investigated the possibility that Rho family members interact with phosphoinositide kinases. We found that both GTP- and GDP-bound Rac1 associate with phosphatidylinositol-4-phosphate 5-kinase in vitro and in vivo. Phosphoinositide 3-kinase also bound to Rac1 and Cdc42Hs, and these interactions were GTP-dependent. Stimulation of Swiss 3T3 cells with platelet-derived growth factor induced the association of PI 3-kinase with Rac in immunoprecipitates. PI 3-kinase activity was also detected in Cdc42 immunoprecipitates from COS7 cells. These results suggest that phosphoinositide kinases are involved in Rho family signal transduction pathways and raise the possibility that the effects of Rho family members on the actin cytoskeleton are mediated in part by phosphoinositide kinases.
引用
收藏
页码:17656 / 17659
页数:4
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