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Novartis Medal Lecture

Rho GTPases and the control of cell behaviour

A. Hall
Biochemical Society Transactions Oct 26, 2005, 33 (5) 891-895; DOI: 10.1042/BST0330891
A. Hall
MRC Laboratory for Molecular Cell Biology and Department of Biochemistry and Molecular Biology, Cancer Research UK Oncogene and Signal Transduction Group, University College London, Gower Street, London WC1E 6BT, U.K.
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Abstract

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-κB (nuclear factor κB) 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.

  • actin
  • GTPase
  • microtubule
  • polarity
  • Rho

Abbreviations: APC, adenomatous polyposis coli; Arp2/3, actin-related protein 2/3; GEF, guanine nucleotide-exchange factor; GSK3, glycogen synthase kinase 3; MAPK, mitogen-activated protein kinase; PAK, p21-activated kinase; (a)PKC, (atypical) protein kinase C; REF, rat embryo fibroblast; SRF, serum-response factor; WASP, Wiskott–Aldrich syndrome protein

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October 2005

Volume: 33 Issue: 5

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Rho GTPases and the control of cell behaviour
A. Hall
Biochemical Society Transactions Oct 2005, 33 (5) 891-895; DOI: 10.1042/BST0330891
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Rho GTPases and the control of cell behaviour
A. Hall
Biochemical Society Transactions Oct 2005, 33 (5) 891-895; DOI: 10.1042/BST0330891

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Keywords

actin
GTPase
microtubule
polarity
Rho

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