The small GTP-binding proteins Rac1 and Cdc42regulate the activity of the JNK/SAPK signaling pathway

阅读量：

137

作者：

Omar A. Coso and Mario Chiariello and Jin-Chen Yu and Hidemi Teramoto and Piero Crespo and Ningzhi Xu and Toru Miki and J. Silvio Gutkind

展开

摘要：

Summary c-Jun amino-terminal kinases (JNKs) and mitogen-activatedprotein 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 Ras 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 Racl 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 Racl and Cdc42 in controlling the JNK signaling pathway.

展开

关键词：

Animals Cercopithecus aethiops Humans Muscle, Skeletal Kidney Cell Line GTP Phosphohydrolases GTP-Binding Proteins cdc42 GTP-Binding Protein, Saccharomyces cerevisiae rac GTP-Binding Proteins