title: SH2 domains recognize specific phosphopeptide sequences.
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-Ile/Pro while another group (SH2 domains of p85, phospholipase C-gamma, and SHPTP2) selected the general motif pTyr-hydrophobic-X-hydrophobic. Individual members of these groups selected unique sequences, except the Src subfamily (Src, Fyn, 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.
authors.affiliation: Cellular and Molecular Physiology Harvard Medical School, Beth Israel Hospital, Boston, Massachusetts 02115.
authors.forename: Z
authors.initials: Z
authors.lastname: Songyang
authors.forename: S E
authors.initials: SE
authors.lastname: Shoelson
authors.forename: M
authors.initials: M
authors.lastname: Chaudhuri
authors.forename: G
authors.initials: G
authors.lastname: Gish
authors.forename: T
authors.initials: T
authors.lastname: Pawson
authors.forename: W G
authors.initials: WG
authors.lastname: Haser
authors.forename: F
authors.initials: F
authors.lastname: King
authors.forename: T
authors.initials: T
authors.lastname: Roberts
authors.forename: S
authors.initials: S
authors.lastname: Ratnofsky
authors.forename: R J
authors.initials: RJ
authors.lastname: Lechleider
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D008969:Molecular Sequence Data; D010748:Phosphopeptides / Q000378:metabolism*; D010766:Phosphorylation; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*
chemical_list: D010748:Phosphopeptides; D016392:Proto-Oncogene Proteins pp60(c-src)