Rho Family GTPases Regulate p38 Mitogen-activated Protein Kinase through the Downstream Mediator Pak1

作者：Shengjia Zhang, Jiahuai Han, Mary Ann Sells, Jonathan Chernoff, Ulla G. Knaus, Richard J. Ulevitch, Gary Bokoch · 发表于：Journal of Biological Chemistry · 年份：1995 · DOI：10.1074/jbc.270.41.23934 · 被引用次数：732 · 研究领域：Melanoma and MAPK Pathways、Protein Kinase Regulation and GTPase Signaling、Cell death mechanisms and regulation

The stress-activated p38 mitogen-activated protein (MAP) kinase defines a subgroup of the mammalian MAP kinases that appear to play a key role in regulating inflammatory responses. Co-expression of constitutively active forms of Rac and Cdc42 leads to activation of p38 while dominant negative Rac and Cdc42 inhibit the ability of interleukin-1 to increase p38 activity. p21-activated kinase 1 (Pak1) is a potential mediator of Rac/Cdc42 signaling, and we observe that Pak1 stimulates p38 activity. A dominant negative Pak1 suppresses both interleukin-1- and Rac/Cdc42-induced p38 activity. Rac and Cdc42 appear to regulate a protein kinase cascade initiated at the level of Pak and leading to activation of p38 and JNK.