THE SMALL GTP-BINDING PROTEINS RAC1 AND CDC42 REGULATE THE ACTIVITY OF THE JNK/SAPK SIGNALING PATHWAY

被引:1574
作者
COSO, OA [1 ]
CHIARIELLO, M [1 ]
YU, JC [1 ]
TERAMOTO, H [1 ]
CRESPO, P [1 ]
XU, NG [1 ]
MIKI, T [1 ]
GUTKIND, JS [1 ]
机构
[1] NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892
关键词
D O I
10.1016/S0092-8674(05)80018-2
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
c-Jun amino-terminal kinases (JNKs) and mitogen-activated protein kinases (MAPKs) are closely related; however, they are independently regulated by a variety of environmental stimuli. Although molecules linking growth factor receptors to MAPKs have been recently identified, little is known about pathways controlling JNK activation. Here, we show that in COS-7 cells, activated Rac1 effectively stimulates MAPK but poorly induces JNK activity. In contrast, mutationally activated Rac1. and Cdc42 GTPases potently activate JNK without affecting MAPK, and oncogenic guanine nucleotide exchange factors for these Rho-like proteins selectively stimulate JNK activity. Furthermore, expression of inhibitory molecules for Rho-related GTPases and dominant negative mutants of Rac1 and Cdc42 block JNK activation by oncogenic exchange factors or after induction by inflammatory cytokines and growth factors. Taken together, these findings strongly support a critical role for Rac1 and Cdc42 in controlling the JNK signaling pathway.
引用
收藏
页码:1137 / 1146
页数:10
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