Cell
Volume 72, Issue 5, 12 March 1993, Pages 767-778
Journal home page for Cell

Article
SH2 domains recognize specific phosphopeptide sequences

https://doi.org/10.1016/0092-8674(93)90404-EGet rights and content

Abstract

A phosphopeptide library was used to determine the sequence specificity of the peptide-binding sites of SH2 domains. One group of SH2 domains (Src, Fyn, Lck, Fgr, Abl, Crk, and Nck) preferred sequences with the general motif pTyr-hydrophilic-hydrophilic-lle/Pro while another group (SH2 domains of p85, phosphollpase C-γ, and SHPTP2) selected the general motif pTyr-hydrophobic-X-hydrophobic. Individual members of these groups selected unique sequences, except the Src subfamily (Src, F́yn, Lck, and Fgr), which all selected the sequence pTyr-Glu-Glu-Ile. The variability in SH2 domain sequences at likely sites of contact provides a structural basis for the phosphopeptide selectivity of these families. Possible in vivo binding sites of the SH2 domains are discussed.

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