Rho GTPases and the control of cell behaviour.
Rho, Rac and Cdc42, three members of the Rho family of small GTPases, each control a signal transduction pathway linking membrane receptors to the assembly and disassembly of the actin cytoskeleton and of associated integrin adhesion complexes. Rho regulates stress fibre and focal adhesion assembly, Rac regulates the formation of lamellipodia protrusions and membrane ruffles, and Cdc42 triggers filopodial extensions at the cell periphery. These observations have led to the suggestion that wherever filamentous actin is used to drive a cellular process, Rho GTPases are likely to play an important regulatory role. Rho GTPases have also been reported to control other cellular activities, such as the JNK (c-Jun N-terminal kinase) and p38 MAPK (mitogen-activated protein kinase) cascades, an NADPH oxidase enzyme complex, the transcription factors NF-kappaB (nuclear factor kappaB) and SRF (serum-response factor), and progression through G1 of the cell cycle. Thus Rho, Rac and Cdc42 can regulate the actin cytoskeleton and gene transcription to promote co-ordinated changes in cell behaviour. We have been analysing the biochemical contributions of Rho GTPases in cell movement and have found that Rac controls cell protrusion, while Cdc42 controls cell polarity.
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MRC Laboratory for Molecular Cell Biology and Department of Biochemistry and Molecular Biology, Cancer Research UK Oncogene and Signal Transduction Group, University College London, London WC1E 6BT, UK. alan.hall@ucl.ac.uk
D000199:Actins / Q000502:physiology; D000818:Animals; D001253:Astrocytes / Q000502:physiology; D002453:Cell Cycle; D002465:Cell Movement / Q000502:physiology; D002468:Cell Physiological Phenomena; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D000199:Actins; D048051:p38 Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins