Phosphorylation-dependent and constitutive activation of Rho proteins by wild-type and oncogenic Vav-2 - PubMed (original) (raw)

Phosphorylation-dependent and constitutive activation of Rho proteins by wild-type and oncogenic Vav-2

K E Schuebel et al. EMBO J. 1998.

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 with 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 in rodent 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 a new 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.

PubMed Disclaimer

Similar articles

Cited by

References

    1. Cell. 1998 May 29;93(5):815-26 - PubMed
    1. Science. 1998 Jan 23;279(5350):558-60 - PubMed
    1. Nature. 1985 Jul 18-24;316(6025):273-5 - PubMed
    1. Mol Cell Biol. 1991 Apr;11(4):1912-20 - PubMed
    1. Cell Growth Differ. 1991 Feb;2(2):95-105 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources