Lck regulates Vav activation of members of the Rho family of GTPases

Author:

Han J1,Das B1,Wei W1,Van Aelst L1,Mosteller R D1,Khosravi-Far R1,Westwick J K1,Der C J1,Broek D1

Affiliation:

1. Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, School of Medicine, University of Southern California, Los Angeles 90033, USA.

Abstract

Vav is a member of a family of oncogene proteins that share an approximately 250-amino-acid motif called a Dbl homology domain. Paradoxically, Dbl itself and other proteins containing a Dbl domain catalyze GTP-GDP exchange for Rho family proteins, whereas Vav has been reported to catalyze GTP-GDP exchange for Ras proteins. We present Saccharomyces cerevisiae genetic data, in vitro biochemical data, and animal cell biological data indicating that Vav is a guanine nucleotide exchange factor for Rho-related proteins, but in similar genetic and biochemical experiments we fail to find evidence that Vav is a guanine nucleotide exchange factor for Ras. Further, we present data indicating that the Lck kinase activates the guanine nucleotide exchange factor and transforming activity of Vav.

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

Reference51 articles.

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4. Differential activation of yeast adenylate cyclase by wildtype and mutant Ras proteins;Broek D.;Cell,1985

5. Vav cooperates with Ras to transform rodent fibroblasts but is not a Ras GDP/GTP exchange factor;Bustelo X. R.;Oncogene,1994

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