A Caltech Library Service

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

Mayer, Bruce J. and Jackson, Peter K. and Van Etten, Richard A. and Baltimore, David (1992) Point mutations in the abl SH2 domain coordinately impair phosphotyrosine binding in vitro and transforming activity in vivo. Molecular and Cellular Biology, 12 (2). pp. 609-618. ISSN 0270-7306. PMCID PMC364250.

PDF - Published Version
See Usage Policy.


Use this Persistent URL to link to this item:


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.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Baltimore, David0000-0001-8723-8190
Additional Information:© 1992 by the American Society for Microbiology. Received 29 July 1991/Accepted 13 November 1991. We thank R. Birge, D. Cowburn, M. Matsuda, and M. Scott for helpful comments on the manuscript. We are extremely grateful to M. Overduin and D. Cowburn, who provided NMR spectra and many discussions on protein structure. This work was supported by Public Health Service grant CA 51462 and National Research Service award CA 08875 from the National Cancer Institute. R.A.V. is a Lucille P. Markey Scholar and was supported in part by the Lucille P. Markey Charitable Trust. NMR facilities at Rockefeller University were purchased with grants from the National Institutes of Health, the National Science Foundation, and the Keck Foundation.
Funding AgencyGrant Number
NIHCA 51462
NIHCA 08875
Lucille P. Markey Charitable TrustUNSPECIFIED
National Cancer InstituteUNSPECIFIED
W. M. Keck FoundationUNSPECIFIED
Issue or Number:2
PubMed Central ID:PMC364250
Record Number:CaltechAUTHORS:MAYmcb92
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:12779
Deposited By: Archive Administrator
Deposited On:23 Dec 2008 16:30
Last Modified:03 Oct 2019 00:31

Repository Staff Only: item control page