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PMID: 7809090 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 26 ·1994-12-20 ·Pages 12629-33

Ye ZS, Baltimore D

Abstract

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.

Related Genes
grb2 vav
MeSH Terms
Adaptor Proteins, Signal Transducing Amino Acid Sequence Animals Cell Cycle Proteins DNA Mutational Analysis GRB2 Adaptor Protein Humans Mice Molecular Sequence Data Peptides/chemistry Protein Binding Proteins/metabolism Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-vav Signal Transduction Structure-Activity Relationship
Chemicals
Adaptor Proteins, Signal Transducing Cell Cycle Proteins GRB2 Adaptor Protein GRB2 protein, human Grb2 protein, mouse Peptides Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-vav VAV1 protein, human Vav1 protein, mouse
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Ye Z S
Rockefeller University, New York, NY 10021.
Baltimore D
References (41)
41 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.91.26.12629
Published
1994-12-20
Pages
12629-33
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC45492
Subset
IM
Grants
NCI NIH HHS · CA51462 · United States
External Links
PubMed source DOI: 10.1073/pnas.91.26.12629 PMC Full Text View journal details
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