Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Ras-GAP controls Rho-mediated cytoskeletal reorganization through its SH3 domain.
Leblanc V
,
Tocque B
,
Delumeau I
.
???displayArticle.abstract???
Proteins of the Ras superfamily, Ras, Rac, Rho, and Cdc42, control the remodelling of the cortical actin cytoskeleton following growth factor stimulation. A major regulator of Ras, Ras-GAP, contains several structural motifs, including an SH3 domain and two SH2 domains, and there is evidence that they harbor a signalling function. We have previously described a monoclonal antibody to the SH3 domain of Ras-GAP which blocks Ras signalling in Xenopus oocytes. We now show that microinjection of this antibody into Swiss 3T3 cells prevents the formation of actin stress fibers stimulated by growth factors or activated Ras, but not membrane ruffling. This inhibition is bypassed by coinjection of activated Rho, suggesting that the Ras-GAP SH3 domain is necessary for endogenous Rho activation. In agreement, the antibody blocks lysophosphatidic acid-induced neurite retraction in differentiated PC12 cells. Furthermore, we demonstrate that microinjection of full-length Ras-GAP triggers stress fiber polymerization in fibroblasts in an SH3-dependent manner, strongly suggesting an effector function besides its role as a Ras downregulator. These results support the idea that Ras-GAP connects the Ras and Rho pathways and, therefore, regulates the actin cytoskeleton through a mechanism which probably does not involve p190 Rho-GAP.
Abdellatif,
An effector-like function of Ras GTPase-activating protein predominates in cardiac muscle cells.
1997, Pubmed
Abdellatif,
An effector-like function of Ras GTPase-activating protein predominates in cardiac muscle cells.
1997,
Pubmed
Bar-Sagi,
Microinjection of the ras oncogene protein into PC12 cells induces morphological differentiation.
1985,
Pubmed
Boguski,
Proteins regulating Ras and its relatives.
1993,
Pubmed
Bokoch,
Emerging concepts in the Ras superfamily of GTP-binding proteins.
1993,
Pubmed
Bryant,
Two SH2 domains of p120 Ras GTPase-activating protein bind synergistically to tyrosine phosphorylated p190 Rho GTPase-activating protein.
1995,
Pubmed
Burbelo,
p190-B, a new member of the Rho GAP family, and Rho are induced to cluster after integrin cross-linking.
1995,
Pubmed
Chardin,
Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2.
1993,
Pubmed
Chavrier,
An immunologist's look at the Rho and Rab GTP-binding proteins.
1993,
Pubmed
Clark,
p120 GAP modulates Ras activation of Jun kinases and transformation.
1997,
Pubmed
Clark,
Differential antagonism of Ras biological activity by catalytic and Src homology domains of Ras GTPase activation protein.
1993,
Pubmed
Duchesne,
Identification of the SH3 domain of GAP as an essential sequence for Ras-GAP-mediated signaling.
1993,
Pubmed
,
Xenbase
Ellis,
Phosphorylation of GAP and GAP-associated proteins by transforming and mitogenic tyrosine kinases.
1990,
Pubmed
Fukumoto,
Molecular cloning and characterization of a novel type of regulatory protein (GDI) for the rho proteins, ras p21-like small GTP-binding proteins.
1990,
Pubmed
Furth,
Monoclonal antibodies to the p21 products of the transforming gene of Harvey murine sarcoma virus and of the cellular ras gene family.
1982,
Pubmed
Gebbink,
Identification of a novel, putative Rho-specific GDP/GTP exchange factor and a RhoA-binding protein: control of neuronal morphology.
1997,
Pubmed
Gosser,
C-terminal binding domain of Rho GDP-dissociation inhibitor directs N-terminal inhibitory peptide to GTPases.
1997,
Pubmed
Gotoh,
Identification of Rap1 as a target for the Crk SH3 domain-binding guanine nucleotide-releasing factor C3G.
1995,
Pubmed
Henkemeyer,
Vascular system defects and neuronal apoptosis in mice lacking ras GTPase-activating protein.
1995,
Pubmed
Hotchin,
The assembly of integrin adhesion complexes requires both extracellular matrix and intracellular rho/rac GTPases.
1995,
Pubmed
Howe,
Lysophosphatidic acid stimulates mitogen-activated protein kinase activation via a G-protein-coupled pathway requiring p21ras and p74raf-1.
1993,
Pubmed
Hu,
Tandem SH2 binding sites mediate the RasGAP-RhoGAP interaction: a conformational mechanism for SH3 domain regulation.
1997,
Pubmed
Huang,
Plasma membrane-targeted ras GTPase-activating protein is a potent suppressor of p21ras function.
1993,
Pubmed
Kozma,
The GTPase-activating protein n-chimaerin cooperates with Rac1 and Cdc42Hs to induce the formation of lamellipodia and filopodia.
1996,
Pubmed
Kozma,
The Ras-related protein Cdc42Hs and bradykinin promote formation of peripheral actin microspikes and filopodia in Swiss 3T3 fibroblasts.
1995,
Pubmed
Kozma,
Rho family GTPases and neuronal growth cone remodelling: relationship between increased complexity induced by Cdc42Hs, Rac1, and acetylcholine and collapse induced by RhoA and lysophosphatidic acid.
1997,
Pubmed
Kundra,
The chemotactic response to PDGF-BB: evidence of a role for Ras.
1995,
Pubmed
Lamarche,
GAPs for rho-related GTPases.
1994,
Pubmed
Mattingly,
Muscarinic receptors transform NIH 3T3 cells through a Ras-dependent signalling pathway inhibited by the Ras-GTPase-activating protein SH3 domain.
1994,
Pubmed
Mayer,
SH3 domains. Minding your p's and q's.
1995,
Pubmed
McGlade,
The N-terminal region of GAP regulates cytoskeletal structure and cell adhesion.
1993,
Pubmed
Medema,
GTPase-activating protein SH2-SH3 domains induce gene expression in a Ras-dependent fashion.
1992,
Pubmed
Mollat,
Non-neutralizing monoclonal antibodies against Ras GTPase-activating protein: production, characterization and use in an enzyme immunometric assay.
1992,
Pubmed
Mulcahy,
Requirement for ras proto-oncogene function during serum-stimulated growth of NIH 3T3 cells.
,
Pubmed
Nakata,
Proliferation and differentiation of PC12 cells were affected by p21ras GTPase activating proteins and its deletion mutant proteins.
1996,
Pubmed
Nishiki,
ADP-ribosylation of the rho/rac proteins induces growth inhibition, neurite outgrowth and acetylcholine esterase in cultured PC-12 cells.
1990,
Pubmed
Nobes,
Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia.
1995,
Pubmed
Nori,
Inhibition of v-src-induced transformation by a GTPase-activating protein.
1991,
Pubmed
Olson,
An essential role for Rho, Rac, and Cdc42 GTPases in cell cycle progression through G1.
1995,
Pubmed
Parker,
A Ras-GTPase-activating protein SH3-domain-binding protein.
1996,
Pubmed
Paterson,
Microinjection of recombinant p21rho induces rapid changes in cell morphology.
1990,
Pubmed
Pomerance,
The Ras-GTPase-activating protein SH3 domain is required for Cdc2 activation and mos induction by oncogenic Ras in Xenopus oocytes independently of mitogen-activated protein kinase activation.
1996,
Pubmed
,
Xenbase
Rey,
Antibodies to synthetic peptide from the residue 33 to 42 domain of c-Ha-ras p21 block reconstitution of the protein with different effectors.
1989,
Pubmed
Ridley,
rho family GTPase activating proteins p190, bcr and rhoGAP show distinct specificities in vitro and in vivo.
1993,
Pubmed
Ridley,
The small GTP-binding protein rac regulates growth factor-induced membrane ruffling.
1992,
Pubmed
Ridley,
The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors.
1992,
Pubmed
Rodriguez-Viciana,
Role of phosphoinositide 3-OH kinase in cell transformation and control of the actin cytoskeleton by Ras.
1997,
Pubmed
Schweighoffer,
Implication of GAP in Ras-dependent transactivation of a polyoma enhancer sequence.
1992,
Pubmed
Settleman,
Molecular cloning of cDNAs encoding the GAP-associated protein p190: implications for a signaling pathway from ras to the nucleus.
1992,
Pubmed
Settleman,
Association between GTPase activators for Rho and Ras families.
1992,
Pubmed
Sudol,
The WW module competes with the SH3 domain?
1996,
Pubmed
Tapon,
Rho, Rac and Cdc42 GTPases regulate the organization of the actin cytoskeleton.
1997,
Pubmed
Tigyi,
Lysophosphatidic acid-induced neurite retraction in PC12 cells: control by phosphoinositide-Ca2+ signaling and Rho.
1996,
Pubmed
Tocque,
Ras-GTPase activating protein (GAP): a putative effector for Ras.
1997,
Pubmed
Trahey,
A cytoplasmic protein stimulates normal N-ras p21 GTPase, but does not affect oncogenic mutants.
1987,
Pubmed
,
Xenbase
van Corven,
Pertussis toxin-sensitive activation of p21ras by G protein-coupled receptor agonists in fibroblasts.
1993,
Pubmed
Wood,
The cytoplasmic raf oncogene induces a neuronal phenotype in PC12 cells: a potential role for cellular raf kinases in neuronal growth factor signal transduction.
1993,
Pubmed
Xu,
The non-catalytic domain of ras-GAP inhibits transformation induced by G protein coupled receptors.
1994,
Pubmed
Yao,
Regulation of the Ras signaling pathway by GTPase-activating protein in PC12 cells.
1995,
Pubmed
Zhang,
Suppression of c-ras transformation by GTPase-activating protein.
1990,
Pubmed
