Rho GTPases: biochemistry and biology.

Approximately one percent of the human genome encodes proteins that either regulate or are regulated by direct interaction with members of the Rho family of small GTPases. Through a series of complex biochemical networks, these highly conserved molecular switches control some of the most fundamental processes of cell biology common to all eukaryotes, including morphogenesis, polarity, movement, and cell division. In the first part of this review, we present the best characterized of these biochemical pathways; in the second part, we attempt to integrate these molecular details into a biological context.

[1]  J. Gutkind,et al.  Signaling from the Small GTP-binding Proteins Rac1 and Cdc42 to the c-Jun N-terminal Kinase/Stress-activated Protein Kinase Pathway , 1996, The Journal of Biological Chemistry.

[2]  Daniel Zicha,et al.  A Role for Cdc42 in Macrophage Chemotaxis , 1998, The Journal of cell biology.

[3]  S. Narumiya,et al.  Citron kinase, a Rho-dependent kinase, induces di-phosphorylation of regulatory light chain of myosin II. , 2003, Molecular biology of the cell.

[4]  Paul Herzmark,et al.  Lipid products of PI(3)Ks maintain persistent cell polarity and directed motility in neutrophils , 2002, Nature Cell Biology.

[5]  Z. Werb,et al.  Role of Rac1 and oxygen radicals in collagenase-1 expression induced by cell shape change. , 1998, Science.

[6]  J. Hartwig,et al.  Type Iα phosphatidylinositol-4-phosphate 5-kinase mediates Rac-dependent actin assembly , 2000, Current Biology.

[7]  E. Sahai,et al.  Cross‐talk between Ras and Rho signalling pathways in transformation favours proliferation and increased motility , 2001, The EMBO journal.

[8]  John G. Collard,et al.  The Rac Exchange Factor Tiam1 Is Required for the Establishment and Maintenance of Cadherin-based Adhesions* , 2004, Journal of Biological Chemistry.

[9]  S. Parkhurst,et al.  Rho1 interacts with p120ctn and alpha-catenin, and regulates cadherin-based adherens junction components in Drosophila. , 2002, Development.

[10]  Y. Jan,et al.  Hippocampal Neuronal Polarity Specified by Spatially Localized mPar3/mPar6 and PI 3-Kinase Activity , 2003, Cell.

[11]  A. Hall,et al.  Guanine nucleotide exchange factors for Rho GTPases: turning on the switch. , 2002, Genes & development.

[12]  Y. Jan,et al.  APC and GSK-3β Are Involved in mPar3 Targeting to the Nascent Axon and Establishment of Neuronal Polarity , 2004, Current Biology.

[13]  John S. Condeelis,et al.  Cofilin Promotes Actin Polymerization and Defines the Direction of Cell Motility , 2004, Science.

[14]  J. Condeelis,et al.  Cofilin takes the lead , 2005, Journal of Cell Science.

[15]  A. Bernards.  GAPs galore! A survey of putative Ras superfamily GTPase activating proteins in man and Drosophila. , 2003, Biochimica et biophysica acta.

[16]  M. Fanto,et al.  Planar polarity from flies to vertebrates , 2004, Journal of Cell Science.

[17]  S. Gygi,et al.  Toca-1 Mediates Cdc42-Dependent Actin Nucleation by Activating the N-WASP-WIP Complex , 2004, Cell.

[18]  M. Kohjima,et al.  Novel Human Homologues of p47phox and p67phox Participate in Activation of Superoxide-producing NADPH Oxidases* , 2003, Journal of Biological Chemistry.

[19]  T. Pawson,et al.  A polarity complex of mPar-6 and atypical PKC binds, phosphorylates and regulates mammalian Lgl , 2003, Nature Cell Biology.

[20]  D. Bar-Sagi,et al.  A Rac1 Effector Site Controlling Mitogenesis through Superoxide Production* , 1998, The Journal of Biological Chemistry.

[21]  Todd Blevins,et al.  RNA silencing systems and their relevance to plant development. , 2005, Annual review of cell and developmental biology.

[22]  M. Matsuda,et al.  Activation of Rac and Cdc42 Video Imaged by Fluorescent Resonance Energy Transfer-Based Single-Molecule Probes in the Membrane of Living Cells , 2002, Molecular and Cellular Biology.

[23]  T. Sakai,et al.  ADP-ribosylation of the rhoA gene product by botulinum C3 exoenzyme causes Swiss 3T3 cells to accumulate in the G1 phase of the cell cycle. , 1993, Oncogene.

[24]  J. Westwick,et al.  Integrin-specific activation of Rac controls progression through the G(1) phase of the cell cycle. , 2001, Molecular cell.

[25]  H. Bellen,et al.  A putative exchange factor for Rho1 GTPase is required for initiation of cytokinesis in Drosophila. , 1999, Genes & development.

[26]  R. Assoian,et al.  Effects of Rho Kinase and Actin Stress Fibers on Sustained Extracellular Signal-Regulated Kinase Activity and Activation of G1 Phase Cyclin-Dependent Kinases , 2003, Molecular and Cellular Biology.

[27]  Richard A. Firtel,et al.  Leading the way: directional sensing through phosphatidylinositol 3-kinase and other signaling pathways , 2003, Journal of Cell Science.

[28]  F. Matsumura,et al.  Specific Localization of Serine 19 Phosphorylated Myosin II during Cell Locomotion and Mitosis of Cultured Cells , 1998, The Journal of cell biology.

[29]  A. Abo,et al.  Interaction of Rac with p67phox and regulation of phagocytic NADPH oxidase activity. , 1994, Science.

[30]  B. Baum,et al.  Myosin II-Dependent Cortical Movement Is Required for Centrosome Separation and Positioning during Mitotic Spindle Assembly , 2004, Cell.

[31]  C. Marshall,et al.  Signals from Ras and Rho GTPases interact to regulate expression of p21Waf1/Cip1 , 1998, Nature.

[32]  A. Ashworth,et al.  An essential role for Rho, Rac, and Cdc42 GTPases in cell cycle progression through G1 , 1995, Science.

[33]  S. Kuroda,et al.  Rac1 and Cdc42 Capture Microtubules through IQGAP1 and CLIP-170 , 2002, Cell.

[34]  T. Ohnishi,et al.  Atypical Protein Kinase C Is Involved in the Evolutionarily Conserved Par Protein Complex and Plays a Critical Role in Establishing Epithelia-Specific Junctional Structures , 2001, The Journal of cell biology.

[35]  Y. Goshima,et al.  Phosphorylation of Collapsin Response Mediator Protein-2 by Rho-kinase , 2000, The Journal of Biological Chemistry.

[36]  Haigen Huang,et al.  Stimulation of erythropoiesis by inhibiting a new hematopoietic death receptor in transgenic zebrafish , 2000, Nature Cell Biology.

[37]  G. Bloom,et al.  IQGAP1, a Rac- and Cdc42-binding Protein, Directly Binds and Cross-links Microfilaments , 1997, The Journal of cell biology.

[38]  R. Treisman,et al.  Actin Dynamics Control SRF Activity by Regulation of Its Coactivator MAL , 2003, Cell.

[39]  T. Kitamura,et al.  MgcRacGAP regulates cortical activity through RhoA during cytokinesis. , 2004, Experimental cell research.

[40]  T. Pawson,et al.  A mammalian PAR-3–PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity , 2000, Nature Cell Biology.

[41]  R. Tuft,et al.  Effects of the Regulatory Light Chain Phosphorylation of Myosin II on Mitosis and Cytokinesis of Mammalian Cells* , 2000, The Journal of Biological Chemistry.

[42]  M. Chen,et al.  EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration , 2004, Nature Cell Biology.

[43]  G. Gundersen,et al.  mDia mediates Rho-regulated formation and orientation of stable microtubules , 2001, Nature Cell Biology.

[44]  渡辺 崇.  Interaction with IQGAP1 links APC to Rac1, Cdc42 and actin filaments during cell polarization and migration , 2005 .

[45]  N. Perrimon,et al.  Apicobasal polarization: epithelial form and function. , 2003, Current opinion in cell biology.

[46]  Anne Müsch,et al.  Microtubule Organization and Function in Epithelial Cells , 2004, Traffic.

[47]  W. V. van Blitterswijk,et al.  Diacylglycerol Kinase θ Binds to and Is Negatively Regulated by Active RhoA* , 1999, The Journal of Biological Chemistry.

[48]  K. Irie,et al.  Roles and modes of action of nectins in cell-cell adhesion. , 2004, Seminars in cell & developmental biology.

[49]  M. Karin,et al.  Selective activation of the JNK signaling cascadeand c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs , 1995, Cell.

[50]  T. Pollard,et al.  Cellular Motility Driven by Assembly and Disassembly of Actin Filaments , 2003, Cell.

[51]  K. Kaibuchi,et al.  Positive role of IQGAP1, an effector of Rac1, in actin-meshwork formation at sites of cell-cell contact. , 2003, Molecular biology of the cell.

[52]  K. Burridge,et al.  RhoA and ROCK Promote Migration by Limiting Membrane Protrusions* , 2003, The Journal of Biological Chemistry.

[53]  Y. Nagai,et al.  PAR‐6 regulates aPKC activity in a novel way and mediates cell‐cell contact‐induced formation of the epithelial junctional complex , 2001, Genes to cells : devoted to molecular & cellular mechanisms.

[54]  Y. Nagashima,et al.  Involvement of ASIP/PAR-3 in the promotion of epithelial tight junction formation. , 2002, Journal of cell science.

[55]  S. Kuroda,et al.  Cdc42, Rac1, and their effector IQGAP1 as molecular switches for cadherin-mediated cell-cell adhesion. , 1999, Biochemical and biophysical research communications.

[56]  N. Perrimon,et al.  Drosophila Jun relays the Jun amino-terminal kinase signal transduction pathway to the Decapentaplegic signal transduction pathway in regulating epithelial cell sheet movement. , 1997, Genes & development.

[57]  Dise Rs.  Epidermal growth factor stimulates intestinal epithelial cell migration through activation of the small GTPase Rac. , 2006 .

[58]  T. Akiyama,et al.  Interaction with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell polarization and migration. , 2004, Developmental cell.

[59]  Erik Sahai,et al.  Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis , 2003, Nature Cell Biology.

[60]  S. Narumiya,et al.  Rho-associated Kinase ROCK Activates LIM-kinase 1 by Phosphorylation at Threonine 508 within the Activation Loop* , 2000, The Journal of Biological Chemistry.

[61]  A. Püschel,et al.  The sequential activity of the GTPases Rap1B and Cdc42 determines neuronal polarity , 2004, Nature Neuroscience.

[62]  A. Hall,et al.  A Conserved Binding Motif Defines Numerous Candidate Target Proteins for Both Cdc42 and Rac GTPases (*) , 1995, The Journal of Biological Chemistry.

[63]  H. Sumimoto,et al.  Molecular mechanism for activation of superoxide-producing NADPH oxidases. , 2003, Molecules and cells.

[64]  J. Ahringer,et al.  CDC-42 controls early cell polarity and spindle orientation in C. elegans , 2001, Current Biology.

[65]  I. Mellman,et al.  Cdc42 controls secretory and endocytic transport to the basolateral plasma membrane of MDCK cells , 1999, Nature Cell Biology.

[66]  S. Narumiya,et al.  Localization of a mammalian homolog of diaphanous, mDia1, to the mitotic spindle in HeLa cells. , 2001, Journal of cell science.

[67]  L. Cassimeris.  The oncoprotein 18/stathmin family of microtubule destabilizers. , 2002, Current opinion in cell biology.

[68]  M. Symons,et al.  Role of Rho Family Proteins in Phospholipase D Activation by Growth Factors* , 1997, The Journal of Biological Chemistry.

[69]  K. Kemphues,et al.  An Atypical PKC Directly Associates and Colocalizes at the Epithelial Tight Junction with ASIP, a Mammalian Homologue of Caenorhabditis elegans Polarity Protein PAR-3 , 1998, The Journal of cell biology.

[70]  M. Cobb,et al.  RhoA Binds to the Amino Terminus of MEKK1 and Regulates Its Kinase Activity* , 2004, Journal of Biological Chemistry.

[71]  R. Assoian,et al.  Nuclear translocation of LIM kinase mediates Rho-Rho kinase regulation of cyclin D1 expression. , 2003, Developmental cell.

[72]  J. Hartwig,et al.  WIP regulates N-WASP-mediated actin polymerization and filopodium formation , 2001, Nature Cell Biology.

[73]  A. Suzuki,et al.  Mammalian Lgl Forms a Protein Complex with PAR-6 and aPKC Independently of PAR-3 to Regulate Epithelial Cell Polarity , 2003, Current Biology.

[74]  E. Fuchs,et al.  Actin cable dynamics and Rho/Rock orchestrate a polarized cytoskeletal architecture in the early steps of assembling a stratified epithelium. , 2002, Developmental cell.

[75]  A. Hall,et al.  Cdc42 regulates GSK-3β and adenomatous polyposis coli to control cell polarity , 2003, Nature.

[76]  Y. Rao,et al.  Both the Establishment and the Maintenance of Neuronal Polarity Require Active Mechanisms Critical Roles of GSK-3β and Its Upstream Regulators , 2005, Cell.

[77]  Elaine Fuchs,et al.  Directed Actin Polymerization Is the Driving Force for Epithelial Cell–Cell Adhesion , 2000, Cell.

[78]  J. Bamburg,et al.  ADF/Cofilin Controls Cell Polarity during Fibroblast Migration , 2003, Current Biology.

[79]  Alan Hall,et al.  Rho GTPases Control Polarity, Protrusion, and Adhesion during Cell Movement , 1999, The Journal of cell biology.

[80]  V. Braga,et al.  Activation of the small GTPase Rac is sufficient to disrupt cadherin-dependent cell-cell adhesion in normal human keratinocytes. , 2000, Molecular biology of the cell.

[81]  L. Lim,et al.  Dcdc42 acts in TGF-beta signaling during Drosophila morphogenesis: distinct roles for the Drac1/JNK and Dcdc42/TGF-beta cascades in cytoskeletal regulation. , 1999, Journal of cell science.

[82]  N. Tapon,et al.  A new Rac target POSH is an SH3‐containing scaffold protein involved in the JNK and NF‐κB signalling pathways , 1998, The EMBO journal.

[83]  Gary G. Borisy,et al.  Mechanism of filopodia initiation by reorganization of a dendritic network , 2003, The Journal of cell biology.

[84]  G. Joberty,et al.  Assembly of Epithelial Tight Junctions Is Negatively Regulated by Par6 , 2002, Current Biology.

[85]  M. Itoh,et al.  Junctional adhesion molecule (JAM) binds to PAR-3 , 2001, The Journal of cell biology.

[86]  C. Waterman-Storer,et al.  Cell motility: can Rho GTPases and microtubules point the way? , 2001, Journal of cell science.

[87]  P. Gierschik,et al.  Stimulation of phospholipase C‐β2 by the Rho GTPases Cdc42Hs and Rac1 , 1998, The EMBO journal.

[88]  S. Narumiya,et al.  Cdc42 and mDia3 regulate microtubule attachment to kinetochores , 2004, Nature.

[89]  C. Halin,et al.  In vivo imaging of lymphocyte trafficking. , 2005, Annual review of cell and developmental biology.

[90]  M. Schwartz,et al.  Timing of cyclin D1 expression within G1 phase is controlled by Rho , 2009, Nature Cell Biology.

[91]  A. Hall,et al.  The Small GTPases Rho and Rac Are Required for the Establishment of Cadherin-dependent Cell–Cell Contacts , 1997, The Journal of cell biology.

[92]  L. Silengo,et al.  Defective Neurogenesis in Citron Kinase Knockout Mice by Altered Cytokinesis and Massive Apoptosis , 2000, Neuron.

[93]  Y. Takai,et al.  trans-Interactions of Nectins Induce Formation of Filopodia and Lamellipodia through the Respective Activation of Cdc42 and Rac Small G Proteins* , 2002, The Journal of Biological Chemistry.

[94]  L. Greene,et al.  POSH acts as a scaffold for a multiprotein complex that mediates JNK activation in apoptosis , 2003, The EMBO journal.

[95]  L. Machesky,et al.  Signalling to actin assembly via the WASP (Wiskott-Aldrich syndrome protein)-family proteins and the Arp2/3 complex. , 2004, The Biochemical journal.

[96]  T. Miki,et al.  Human Ect2 Is an Exchange Factor for Rho Gtpases, Phosphorylated in G2/M Phases, and Involved in Cytokinesis , 1999, The Journal of cell biology.

[97]  R. Stancou,et al.  Protein kinase A phosphorylation of RhoA mediates the morphological and functional effects of cyclic AMP in cytotoxic lymphocytes. , 1996, The EMBO journal.

[98]  J. Lambeth.  Nox/Duox family of nicotinamide adenine dinucleotide (phosphate) oxidases , 2002, Current opinion in hematology.

[99]  K. Jakobs,et al.  Activation of Type I Phosphatidylinositol 4-Phosphate 5-Kinase Isoforms by the Rho GTPases, RhoA, Rac1, and Cdc42* , 2004, Journal of Biological Chemistry.

[100]  D. Morrison,et al.  Regulation of MAP kinase signaling modules by scaffold proteins in mammals. , 2003, Annual review of cell and developmental biology.

[101]  Wei Lu,et al.  Directional Sensing Requires Gβγ-Mediated PAK1 and PIXα-Dependent Activation of Cdc42 , 2003, Cell.

[102]  Andrea Disanza,et al.  Abi1 is essential for the formation and activation of a WAVE2 signalling complex , 2004, Nature Cell Biology.

[103]  A. Hall,et al.  Association of CNK1 with Rho Guanine Nucleotide Exchange Factors Controls Signaling Specificity Downstream of Rho , 2005, Current Biology.

[104]  S. Narumiya,et al.  Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis , 2005, The Journal of cell biology.

[105]  K. Hahn,et al.  Localized Rac activation dynamics visualized in living cells. , 2000, Science.

[106]  A. Iwamatsu,et al.  The exocyst complex binds the small GTPase RalA to mediate filopodia formation , 2002, Nature Cell Biology.

[107]  S. Bagrodia,et al.  Activation of phosphoinositide 3-kinase activity by Cdc42Hs binding to p85. , 1994, The Journal of biological chemistry.

[108]  Yue Zhang,et al.  Regulation of Cell Polarity and Protrusion Formation by Targeting RhoA for Degradation , 2003, Science.

[109]  M. Okada,et al.  Activation of Cdc42 by trans interactions of the cell adhesion molecules nectins through c-Src and Cdc42-GEF FRG , 2004, The Journal of cell biology.

[110]  M. Chou,et al.  Cdc42 Promotes G1 Progression through p70 S6 Kinase-mediated Induction of Cyclin E Expression* , 2003, Journal of Biological Chemistry.

[111]  H. Kotani,et al.  Regulation of Cell–Cell Adhesion by Rac and Rho Small G Proteins in MDCK Cells , 1997, The Journal of cell biology.

[112]  Michael F. Olson,et al.  RAS and RHO GTPases in G1-phase cell-cycle regulation , 2004, Nature Reviews Molecular Cell Biology.

[113]  J. Baldassare,et al.  RhoA Stimulates p27Kip Degradation through Its Regulation of Cyclin E/CDK2 Activity* , 1999, The Journal of Biological Chemistry.

[114]  J. Ahringer.  Control of cell polarity and mitotic spindle positioning in animal cells. , 2003, Current opinion in cell biology.

[115]  B. Volkman,et al.  Cdc42 regulates the Par-6 PDZ domain through an allosteric CRIB-PDZ transition. , 2004, Molecular cell.

[116]  Gary G. Borisy,et al.  Formation of filopodia-like bundles in vitro from a dendritic network , 2003, The Journal of cell biology.

[117]  Anirban Datta,et al.  Epithelial polarity and tubulogenesis in vitro. , 2003, Trends in cell biology.

[118]  S. Narumiya,et al.  A New Look at Rho GTPases in the Cell Cycle: Their Role in Kinetochore-Microtubule Attachment , 2004, Cell cycle.

[119]  C. Nobes,et al.  Activation of the small GTPase Cdc42 by the inflammatory cytokines TNF(alpha) and IL-1, and by the Epstein-Barr virus transforming protein LMP1. , 1999, Journal of cell science.

[120]  K. Hahn,et al.  Spatial and Temporal Analysis of Rac Activation during Live Neutrophil Chemotaxis , 2002, Current Biology.

[121]  A. Hall,et al.  Rho GTPases in cell biology , 2002, Nature.

[122]  M. Glotzer,et al.  Animal cell cytokinesis. , 2001, Annual review of cell and developmental biology.

[123]  J. Baldassare,et al.  Ras-stimulated Extracellular Signal-related Kinase 1 and RhoA Activities Coordinate Platelet-derived Growth Factor-induced G1 Progression through the Independent Regulation of Cyclin D1 and p27KIP1 * , 1997, The Journal of Biological Chemistry.

[124]  C. Der,et al.  Integration of Rac-dependent Regulation of Cyclin D1 Transcription through a Nuclear Factor-κB-dependent Pathway* , 1999, The Journal of Biological Chemistry.

[125]  Frits Michiels,et al.  Matrix-dependent Tiam1/Rac Signaling in Epithelial Cells Promotes Either Cell–Cell Adhesion or Cell Migration and Is Regulated by Phosphatidylinositol 3-Kinase , 1998, The Journal of cell biology.

[126]  Sulin Wu,et al.  Cytosolic Retention of Phosphorylated Extracellular Signal-Regulated Kinase and a Rho-Associated Kinase-Mediated Signal Impair Expression of p21Cip1/Waf1 in Phorbol 12-Myristate-13- Acetate-Induced Apoptotic Cells , 2002, Molecular and Cellular Biology.

[127]  K. Fujisawa,et al.  Role of citron kinase as a target of the small GTPase Rho in cytokinesis , 1998, Nature.

[128]  S. Reed,et al.  Role for the Rho-family GTPase Cdc42 in yeast mating-pheromone signal pathway , 1995, Nature.

[129]  C. Der,et al.  Rac regulation of transformation, gene expression, and actin organization by multiple, PAK-independent pathways , 1997, Molecular and cellular biology.

[130]  F. Alt,et al.  Cdc42 is required for PIP2-induced actin polymerization and early development but not for cell viability , 2000, Current Biology.

[131]  John G. Collard,et al.  Inhibition of invasion of epithelial cells by Tiam1-Rac signaling. , 1997, Science.

[132]  A. Koff,et al.  Rho Activity Can Alter the Translation of p27 mRNA and Is Important for RasV12-induced Transformation in a Manner Dependent on p27 Status* , 2002, The Journal of Biological Chemistry.

[133]  R. Bravo,et al.  Activation of the nuclear factor-kappaB by Rho, CDC42, and Rac-1 proteins. , 1997, Genes & development.

[134]  J. Segall,et al.  The great escape: when cancer cells hijack the genes for chemotaxis and motility. , 2005, Annual review of cell and developmental biology.

[135]  A. Hall,et al.  Integrin-Mediated Activation of Cdc42 Controls Cell Polarity in Migrating Astrocytes through PKCζ , 2001, Cell.

[136]  K. Kaibuchi,et al.  CRMP-2 binds to tubulin heterodimers to promote microtubule assembly , 2002, Nature Cell Biology.

[137]  Anirban Datta,et al.  Beta1-integrin orients epithelial polarity via Rac1 and laminin. , 2004, Molecular biology of the cell.

[138]  A. Martinez-Arias,et al.  Dynamic actin-based epithelial adhesion and cell matching during Drosophila dorsal closure , 2000, Current Biology.

[139]  B. Olofsson,et al.  Rho guanine dissociation inhibitors: pivotal molecules in cellular signalling. , 1999, Cellular signalling.

[140]  S. Zigmond.  Formin-induced nucleation of actin filaments. , 2004, Current opinion in cell biology.

[141]  W. Simonds,et al.  Signaling from G Protein-coupled Receptors to c-Jun Kinase Involves Subunits of Heterotrimeric G Proteins Acting on a Ras and Rac1-dependent Pathway (*) , 1996, The Journal of Biological Chemistry.

[142]  S. Narumiya,et al.  A New Look at Rho GTPases in Cell Cycle Role in Kinetochore-Microtubule Attachment , 2004 .

[143]  A. Hall,et al.  Rho GTPases and their effector proteins. , 2000, The Biochemical journal.

[144]  Gary G. Borisy,et al.  Arp2/3 Complex and Actin Depolymerizing Factor/Cofilin in Dendritic Organization and Treadmilling of Actin Filament Array in Lamellipodia , 1999, The Journal of cell biology.

[145]  K. Kozminski,et al.  Cdc42 Interacts with the Exocyst and Regulates Polarized Secretion* , 2001, The Journal of Biological Chemistry.

[146]  Alexandre V. Podtelejnikov,et al.  Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck , 2002, Nature.

[147]  A. Hall,et al.  Cdc42 controls the polarity of the actin and microtubule cytoskeletons through two distinct signal transduction pathways , 2005, Journal of Cell Science.

[148]  Ken Jacobson,et al.  JNK phosphorylates paxillin and regulates cell migration , 2003, Nature.

[149]  Thomas D Pollard,et al.  Cellular Motility Driven by Assembly and Disassembly of Actin Filaments , 2003, Cell.

[150]  K. Kaibuchi,et al.  GSK-3β Regulates Phosphorylation of CRMP-2 and Neuronal Polarity , 2005, Cell.

[151]  Marc D. H. Hansen,et al.  Spatio-temporal regulation of Rac1 localization and lamellipodia dynamics during epithelial cell-cell adhesion. , 2002, Developmental cell.

[152]  A. Hall,et al.  Rho GTPases in transformation and metastasis. , 2002, Advances in cancer research.

[153]  Anne J. Ridley,et al.  ROCKs: multifunctional kinases in cell behaviour , 2003, Nature Reviews Molecular Cell Biology.

[154]  P. Crespo,et al.  The small GTP-binding proteins Rac1 and Cdc42regulate the activity of the JNK/SAPK signaling pathway , 1995, Cell.

[155]  M. Kirschner,et al.  CR16 forms a complex with N-WASP in brain and is a novel member of a conserved proline-rich actin-binding protein family , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[156]  J. Saras,et al.  Rho GTPases have diverse effects on the organization of the actin filament system. , 2004, The Biochemical journal.

[157]  S. Narumiya,et al.  Rho-kinase/ROCK is involved in cytokinesis through the phosphorylation of myosin light chain and not ezrin/radixin/moesin proteins at the cleavage furrow , 2000, Oncogene.

[158]  K. Alitalo,et al.  The lymphatic vasculature: recent progress and paradigms. , 2005, Annual review of cell and developmental biology.

[159]  S. Noselli,et al.  Coupling of Jun amino-terminal kinase and Decapentaplegic signaling pathways in Drosophila morphogenesis. , 1997, Genes & development.

[160]  G. Borisy,et al.  Cell Migration: Integrating Signals from Front to Back , 2003, Science.

[161]  A. Hall,et al.  Rac/Cdc42 and p65PAK Regulate the Microtubule-destabilizing Protein Stathmin through Phosphorylation at Serine 16* , 2001, The Journal of Biological Chemistry.