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Titolo:
Cdc42 is required for PIP2-induced actin polymerization and early development but not for cell viability
Autore:
Chen, F; Ma, L; Parrini, MC; Mao, X; Lopez, M; Wu, C; Marks, PW; Davidson, L; Kwiatkowski, DJ; Kirchhausen, T; Orkin, SH; Rosen, FS; Mayer, BJ; Kirschner, MW; Alt, FW;
Indirizzi:
Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 Med, Ctr Blood Res, Boston, MA 02115 USA Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 ch Med, Dept Genet, Boston, MA 02115 USA Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 ed, Dept Cell Biol, Boston, MA 02115 USA Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 robiol & Mol Genet, Boston, MA 02115 USA Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 h Med, Dept Pediat, Boston, MA 02115 USA Childrens Hosp, Mol Med Lab, Boston, MA 02115 USA Childrens Hosp Boston MA USA 02115 osp, Mol Med Lab, Boston, MA 02115 USA Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA Childrens Hosp Boston MA USA 02115 Hughes Med Inst, Boston, MA 02115 USA Harvard Univ, Brigham & Womens Hosp, Sch Med, Genet Lab,Hematol Div, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 et Lab,Hematol Div, Boston, MA 02115 USA
Titolo Testata:
CURRENT BIOLOGY
fascicolo: 13, volume: 10, anno: 2000,
pagine: 758 - 765
SICI:
0960-9822(20000629)10:13<758:CIRFPA>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
WISKOTT-ALDRICH SYNDROME; GTPASE-BINDING DOMAIN; RHO-FAMILY GTPASE; ARP2/3 COMPLEX; PROTEIN CDC42; N-WASP; DEPOLYMERIZING PROTEIN; GENOMIC ORGANIZATION; RAS TRANSFORMATION; CYCLE PROGRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Alt, FW Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA HarvardUniv Boston MA USA 02115 Blood Res, Boston, MA 02115 USA
Citazione:
F. Chen et al., "Cdc42 is required for PIP2-induced actin polymerization and early development but not for cell viability", CURR BIOL, 10(13), 2000, pp. 758-765

Abstract

Background: Cdc42 and other Rho GTPases are conserved from yeast to humansand are thought to regulate multiple cellular functions by inducing coordinated changes in actin reorganization and by activating signaling pathways leading to specific gene expression. Direct evidence implicating upstream signals and components that regulate Cdc42 activity or for required roles ofCdc42 in activation of downstream protein kinase signaling cascades is minimal, however. Also, whereas genetic analyses have shown that Cdc42 is essential for cell viability in yeast, its potential roles in the growth and development of mammalian cells have not been directly assessed. Results: To elucidate potential functions of Cdc42 mammalian cells, we used gene-targeted mutation to inactivate Cdc42 in mouse embryonic stem (ES) cells and in the mouse germline. Surprisingly, Cdc42-deficient ES cells exhibited normal proliferation and phosphorylation of mitogen- and stress-activated protein kinases. Yet Cdc42 deficiency caused very early embryonic lethality in mice and led to aberrant actin cytoskeletal organization in ES cells, Moreover, extracts from Cdc42-deficient cells failed to support phosphatidylinositol 4,5-bisphosphate (PIP2)-induced actin polymerization. Conclusions: Our studies clearly demonstrate that Cdc42 mediates PIP2-induced actin assembly, and document a critical and unique role for Cdc42 in this process. Moreover, we conclude that, unexpectedly, Cdc42 is not necessary for viability or proliferation of mammalian early embryonic cells. Cdc42 is, however, absolutely required for early mammalian development. (C) 2000 Elsevier Science Ltd. All rights reserved.

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Documento generato il 16/07/20 alle ore 18:21:29