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PMID: 1370711 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Point mutations in the abl SH2 domain coordinately impair phosphotyrosine binding in vitro and transforming activity in vivo.

Molecular and cellular biology ·Vol. 12 ·No. 2 ·1992-02-00 ·Pages 609-18

Mayer BJ, Jackson PK, Van Etten RA, Baltimore D

Abstract

We have constructed a series of point mutations in the highly conserved FLVRES motif of the src homology 2 (SH2) domain of the abl tyrosine kinase. Mutant SH2 domains were expressed in bacteria, and their ability to bind to tyrosine-phosphorylated proteins was examined in vitro. Three mutants were greatly reduced in their ability to bind both phosphotyrosine itself and tyrosine-phosphorylated cellular proteins. All of the mutants that retained activity bound to the same set of tyrosine-phosphorylated proteins as did the wild type, suggesting that binding specificity was unaffected. These results implicate the FLVRES motif in direct binding to phosphotyrosine. When the mutant SH2 domains were inserted into an activated abl kinase and expressed in murine fibroblasts, decreased in vitro phosphotyrosine binding correlated with decreased transforming ability. This finding implies that SH2-phosphotyrosine interactions are involved in transmission of positive growth signals by the nonreceptor tyrosine kinases, most likely via the assembly of multiprotein complexes with other tyrosine-phosphorylated proteins.

Related Genes
abl
MeSH Terms
Amino Acid Sequence Binding Sites Cell Line Cell Transformation, Neoplastic/genetics Cell Transformation, Viral/genetics,physiology Cloning, Molecular DNA Mutational Analysis Humans Immunoblotting Magnetic Resonance Spectroscopy Molecular Sequence Data Oncogene Proteins v-abl/genetics,metabolism Phosphotyrosine Retroviridae/genetics Tyrosine/analogs & derivatives,metabolism
Chemicals
Oncogene Proteins v-abl Phosphotyrosine Tyrosine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Mayer B J
Rockefeller University, New York, New York 10021.
Jackson P K
Van Etten R A
Baltimore D
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52 references, click to expand
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.12.2.609-618.1992
Published
1992-02-00
Pages
609-18
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC364250
Subset
IM
Grants
NCI NIH HHS · CA 08875 · United States
NCI NIH HHS · CA 51462 · United States
External Links
PubMed source DOI: 10.1128/mcb.12.2.609-618.1992 PMC Full Text View journal details
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