Cdc42 and PAK-mediated signaling leads to Jun kinase and p38 mitogen-activated protein kinase activation.
The PAK family of protein kinases has been suggested as a potential target of the Cdc42 and Rac GTPases based on studies in vitro. We show that PAK-3 is activated by Cdc42 in vivo. Both, activated (GTPase-defective) Cdc42 and a constitutively active PAK-3 mutant stimulated the activity of Jun kinase 1 (JNK1) in transfected cells. Activated Cdc42 also stimulated the activity of the related p38 mitogen-activated protein kinase but was a less effective activator of ERK2. The effect of Cdc42 on JNK activity was similar to that of the potent inflammatory cytokine interleukin-1 (IL-1). The observation that a dominant-negative Cdc42 mutant inhibited IL-1 activation of JNK1 indicates a role for Cdc42 in IL-1 signaling. These results suggest that Cdc42 and PAK may mediate the effects of cytokines on transcriptional regulation.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D007700:Kinetics; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D010710:Phosphates / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae; D054462:p21-Activated Kinases
D018797:Cell Cycle Proteins; D010710:Phosphates; D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate; C515911:PAK3 protein, human; C515912:Pak3 protein, mouse; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae