SH2 domains recognize specific phosphopeptide sequences

Songyang Zhou, Steven E. Shoelson, Manas Chaudhuri, Gerald Gish, Tony Pawson, Wayne G. Haser, Fred King, Tom Roberts, Sheldon Ratnofsky, Robert J. Lechleider, Benjamin G. Neel, Raymond B. Birge, J. Eduardo Fajardo, Margaret M. Chou, Hidesaburo Hanafusa, Brian Schaffhausen, Lewis C. Cantley

Research output: Contribution to journalArticlepeer-review

2391 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)767-778
Number of pages12
Issue number5
StatePublished - Mar 12 1993
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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