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Published December 20, 1994 | Published
Journal Article Open

Binding of Vav to Grb2 through dimerization of Src homology 3 domains


The protooncogenic protein Vav has the structure of an intracellular signal transducer. It is exclusively expressed in cells of hematopoietic lineage and plays a crucial role in hematopoietic cell differentiation. Here we report that both in cell extracts and within intact mammalian cells Vav binds to Grb2 (Sem-5/ASH/Drk), an adaptor molecule which plays a key role in Ras activation. The interaction became evident from a yeast two-hybrid screen and its specificity was demonstrated by in vitro binding assays. It is mediated by an unusual protein-protein binding reaction: dimerization of specific intact Src homology 3 domains of each of the partners. Signaling during hematopoietic lineage differentiation may therefore involve the tissue-specific signal transducer Vav linking into the ubiquitous pathway involving Grb2 and ultimately Ras.

Additional Information

© 1994 by the National Academy of Sciences. Contributed by David Baltimore, June 30, 1994. We thank Drs. R. Brent, L. Ron, R. Finley, and E. Golemis for the yeast two-hybrid system and technical advice; Dr. J. M. Adams for murine Vav cDNA; and Dr. R. A. Weinberg for Grb2 constructs. We are grateful to Drs. R. Ren, G. Chen, K. Alexandropoulos, W. Pear, and other members of our laboratory for providing reagents, technical assistance, and helpful discussions. Z.-S.Y. is a Special Fellow of the Leukemia Society of America. This work was supported by a U.S. Public Health Service Grant CA51462 to D.B. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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August 22, 2023
August 22, 2023