SH2 domains recognize specific phosphopeptide sequences.
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.
Songyang
Z
Z
Cellular and Molecular Physiology Harvard Medical School, Beth Israel Hospital, Boston, Massachusetts 02115.
Shoelson
S E
SE
Chaudhuri
M
M
Gish
G
G
Pawson
T
T
Haser
W G
WG
King
F
F
Roberts
T
T
Ratnofsky
S
S
Lechleider
R J
RJ
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*
D010748:Phosphopeptides; D016392:Proto-Oncogene Proteins pp60(c-src)