Rho family GTPases regulate p38 mitogen-activated protein kinase through the downstream mediator Pak1.
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.
Zhang
S
S
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
Han
J
J
Sells
M A
MA
Chernoff
J
J
Knaus
U G
UG
Ulevitch
R J
RJ
Bokoch
G M
GM
D000595:Amino Acid Sequence; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D002460:Cell Line; D002522:Chlorocebus aethiops; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000096:biosynthesis*; D019204:GTP-Binding Proteins / Q000096:biosynthesis*; D006367:HeLa Cells; D006801:Humans; D020930:MAP Kinase Kinase Kinases; D008322:Mammals; D020929:Mitogen-Activated Protein Kinase Kinases; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins
D018797:Cell Cycle Proteins; D011994:Recombinant Proteins; D011494:Protein Kinases; C515903:PAK1 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020930:MAP Kinase Kinase Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae; D020744:rac GTP-Binding Proteins