Rac and Cdc42 induce actin polymerization and G1 cell cycle progression independently of p65PAK and the JNK/SAPK MAP kinase cascade.
Rac and Cdc42 regulate a variety of responses in mammalian cells including formation of lamellipodia and filopodia, activation of the JNK MAP kinase cascade, and induction of G1 cell cycle progression. Rac is also one of the downstream targets required for Ras-induced malignant transformation. Rac and Cdc42 containing a Y40C effector site substitution no longer intact with the Ser/Thr kinase p65PAK and are unable to activate the JNK MAP kinase pathway. However, they still induce cytoskeletal changes and G1 cell cycle progression. Rac containing an F37A effector site substitution, on the other hand, no longer interacts with the Ser/Thr kinase p160ROCK and is unable to induce lamellipodia or G1 progression. We conclude that Rac and Cdc42 control MAP kinase pathways and actin cytoskeleton organization independently through distinct downstream targets.
Department of Biochemistry, University College London, United Kingdom.
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Lamarche
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Tapon
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Stowers
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Burbelo
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Aspenström
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Bridges
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Chant
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Hall
D016475:3T3 Cells; D000199:Actins / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D004261:DNA Replication; D004789:Enzyme Activation; D016193:G1 Phase / Q000502:physiology*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology*; D020690:GTPase-Activating Proteins; D016023:Integrins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011108:Polymers; D011494:Protein Kinases / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D011554:Pseudopodia / Q000648:ultrastructure; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection; D020764:cdc42 GTP-Binding Protein; D054462:p21-Activated Kinases; D020703:ras GTPase-Activating Proteins
D000199:Actins; D018797:Cell Cycle Proteins; D020690:GTPase-Activating Proteins; D016023:Integrins; D011108:Polymers; D011506:Proteins; D011993:Recombinant Fusion Proteins; D020703:ras GTPase-Activating Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C482562:Map2k4 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein