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Titolo:
Requirement for C3G-dependent Rap1 activation for cell adhesion and embryogenesis
Autore:
Ohba, Y; Ikuta, K; Ogura, A; Matsuda, J; Mochizuki, N; Nagashima, K; Kurokawa, K; Mayer, BJ; Maki, K; Miyazaki, J; Matsuda, M;
Indirizzi:
Osaka Univ, Dept Tumor Virol, Res Inst Microbial Dis, Suita, Osaka 5650871, Japan Osaka Univ Suita Osaka Japan 5650871 ial Dis, Suita, Osaka 5650871, Japan Kyoto Univ, Dept Med Chem, Grad Sch Med, Kyoto 6068501, Japan Kyoto Univ Kyoto Japan 6068501 Chem, Grad Sch Med, Kyoto 6068501, Japan Natl Inst Infect Dis, Dept Vet Sci, Tokyo 1628640, Japan Natl Inst Infect Dis Tokyo Japan 1628640 t Vet Sci, Tokyo 1628640, Japan Natl Cardiovasc Ctr, Inst Res, Dept Struct Anal, Suita, Osaka 5658565, Japan Natl Cardiovasc Ctr Suita Osaka Japan 5658565 Suita, Osaka 5658565, Japan Hokkaido Univ, Lab Mol & Cellular Pathol, Dept Neurosci, Sapporo, Hokkaido0608638, Japan Hokkaido Univ Sapporo Hokkaido Japan 0608638 poro, Hokkaido0608638, Japan Tokyo Med & Dent Univ, Dept Immune Regulat, Tokyo 1138519, Japan Tokyo Med& Dent Univ Tokyo Japan 1138519 Regulat, Tokyo 1138519, Japan Osaka Univ, Sch Med, Dept Physiol Chem & Nutr, Suita, Osaka 5650871, JapanOsaka Univ Suita Osaka Japan 5650871 & Nutr, Suita, Osaka 5650871, Japan Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Farmington, CT 06030 USA Univ Connecticut Farmington CT USA 06030 v Biol, Farmington, CT 06030 USA
Titolo Testata:
EMBO JOURNAL
fascicolo: 13, volume: 20, anno: 2001,
pagine: 3333 - 3341
SICI:
0261-4189(20010702)20:13<3333:RFCRAF>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
NUCLEOTIDE-RELEASING FACTOR; RAS-DEPENDENT ACTIVATION; EXCHANGE FACTOR C3G; SMALL G-PROTEIN; R-RAS; TYROSINE PHOSPHORYLATION; KINASE ACTIVATION; BINDING PROTEINS; HELPER-FREE; MAP KINASE;
Keywords:
C3G; cell adhesion; cell migration; knockout mouse; Rap1;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
73
Recensione:
Indirizzi per estratti:
Indirizzo: Matsuda, M Osaka Univ, Dept Tumor Virol, Res Inst Microbial Dis, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan Osaka Univ 2-2 Yamadaoka Suita Osaka Japan 5650871 50871, Japan
Citazione:
Y. Ohba et al., "Requirement for C3G-dependent Rap1 activation for cell adhesion and embryogenesis", EMBO J, 20(13), 2001, pp. 3333-3341

Abstract

C3G is a guanine nucleotide exchange factor (GEF) for Rap1, and is activated via Crk adaptor protein. To understand the physiological role of C3G, wegenerated C3G knockout mice. C3G(-/-) homozygous mice died before embryonic day 7.5. The lethality was rescued by the expression of the human C3G transgene, which could be excised upon the expression of Cre recombinase, Fromthe embryo of this mouse, we prepared fibroblast cell lines, MEF-hC3G. Expression of Cre abolished the expression of C3G in MEF-hC3G and inhibited cell adhesion-induced activation of Rap1. The Cre-expressing MEF-hC3G showed impaired cell adhesion, delayed cell spreading and accelerated cell migration. The accelerated cell migration was suppressed by the expression of active Rap1, Rap2 and R-Ras, Expression of Epac and CalDAG-GEFI, GEFs for Rap1,also suppressed the accelerated migration of the CSG-deficient cells. Thisobservation indicated that Rap1 activation was sufficient to complement the C3G deficiency. In conclusion, C3G-dependent activation of Rap1 is required for adhesion and spreading of embryonic fibroblasts and for the early embryogenesis of the mouse.

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Documento generato il 23/01/20 alle ore 03:55:34