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Titolo:
Phosphorylation-dependent and constitutive activation of Rho proteins by wild-type and oncogenic Vav-2
Autore:
Schuebel, KE; Movilla, N; Rosa, JL; Bustelo, XR;
Indirizzi:
SUNY Stony Brook Hosp, Dept Pathol, Stony Brook, NY 11794 USA SUNY Stony Brook Hosp Stony Brook NY USA 11794 Stony Brook, NY 11794 USA
Titolo Testata:
EMBO JOURNAL
fascicolo: 22, volume: 17, anno: 1998,
pagine: 6608 - 6621
SICI:
0261-4189(19981116)17:22<6608:PACAOR>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
GDP/GTP EXCHANGE FACTOR; PROTOONCOGENE PRODUCT; TYROSINE PHOSPHORYLATION; BINDING PROTEIN; RAS; GTPASES; FAMILY; IDENTIFICATION; PATHWAYS; CELLS;
Keywords:
GDP-GTP exchange factors; phosphorylation; Rac; Rho; Vav family;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
25
Recensione:
Indirizzi per estratti:
Indirizzo: Bustelo, XR SUNY94tony Brook Hosp, Dept Pathol, Level 2,Room 718-B, Stony Brook, NY 117 SUNY Stony Brook Hosp Level 2,Room 718-B Stony Brook NY USA 11794
Citazione:
K.E. Schuebel et al., "Phosphorylation-dependent and constitutive activation of Rho proteins by wild-type and oncogenic Vav-2", EMBO J, 17(22), 1998, pp. 6608-6621

Abstract

We show here that Vav-2, a member of the Vav family of oncoproteins, acts as a guanosine nucleotide exchange factor (GEF) for RhoG and RhoA-like GTPases in a phosphotyrosine-dependent manner. Moreover, we show that Vav-2 oncogenic activation correlates with the acquisition of phosphorylation-independent exchange activity. In vivo, wild-type Vav-2 is activated oncogenically by tyrosine kinases, an effect enhanced further by co-expression of RhoA,Likewise, the Vav-2 oncoprotein synergizes,vith RhoA and RhoB proteins in cellular transformation. Transient transfection assays in NIH-3T3 cells show that phosphorylated wild-type Vav-2 and the Vav-2 oncoprotein induce cytoskeletal changes resembling those observed by the activation of the RhoG pathway, In contrast, the constitutive expression of the Vav-2 oncoprotein inrodent fibroblasts leads to major alterations in cell morphology and to highly enlarged cells in which karyokinesis and cytokinesis frequently are uncoupled, These results identify a regulated GEF for the RhoA subfamily, provide a biochemical explanation for vav family oncogenicity, and establish anew signaling model in which specific Vav-like proteins couple tyrosine kinase signals with the activation of distinct subsets of the Rho/Rac family of GTPases.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 10:34:15