test Browse by Author Names Browse by Titles of Works Browse by Subjects of Works Browse by Issue Dates of Works

Advanced Search
& Collections
Issue Date   
Sign on to:   
Receive email
My Account
authorized users
Edit Profile   
About T-Space   

T-Space at The University of Toronto Libraries >
Mount Sinai Hospital  >
Pawson, Tony >

Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/9433

Title: SH2 domain specificity and activity modified by a single residue
Authors: Marengere, Luc E. M.
Zhou, Songyang
Gish, Gerald D.
Schaller, Michael D.
Parsons, J. Thomas
Stern, Michael J.
Cantley, Lewis C.
Pawson, Tony
Keywords: Adaptor Proteins, Signal Transducing
Caenorhabditis elegans Proteins
Drosophila Proteins
Focal Adhesion Protein-Tyrosine Kinases
GRB2 Adaptor Protein
Issue Date: 1994
Publisher: Nature Publishing Group
Citation: Nature. 1994 Jun 9;369(6480):502-5.
Abstract: Many intracellular targets of protein-tyrosine kinases possess Src homology 2 (SH2) domains that directly recognize phosphotyrosine- containing sites on autophosphorylated growth factor receptors and cytoplasmic proteins, and thereby mediate the activation of biochemical signalling pathways1 -7. SH2 domains possess relatively well conserved residues that form the phosphotyrosinebinding pocket8-11, and more variable residues that are implicated in determining binding specificity by recognition of the three amino acids carboxy-terminal to phosphotyrosine (the +1 to +3 positions)5,7,12,13. One such residue, occupying the EF1 position of the +3-binding pocket, is a Thr in the SH2 domain of the Src tyrosine kinase 12, but is predicted to be a Trp in the SH2 domain of the Sem-5/drk/Grb2 adaptor protein5. Here we report that changing this residue in the Src SH2 domain from Thr to Trp switches its selectivity to resemble that of the Sem-5/drk/Grb2 SH2 domain. Furthermore, this mutant Src SH2 domain effectively substitutes for the SH2 domain of the Sem-5 protein in activation of the Ras pathway in vivo. These results identify a residue that can modify SH2 selectivity, and indicate that the biological activity of an SH2 domain correlates with its binding specificity.
URI: http://www.nature.com
Appears in Collections:Pawson, Tony
Pawson, Tony

Files in This Item:

File Description SizeFormat
Bidirectional signalling through the EPH.pdf598.68 kBAdobe PDF

This item is licensed under a Creative Commons License
Creative Commons

Items in T-Space are protected by copyright, with all rights reserved, unless otherwise indicated.