TY - JOUR
T1 - SH2 domains recognize specific phosphopeptide sequences
AU - Zhou, Songyang
AU - Shoelson, Steven E.
AU - Chaudhuri, Manas
AU - Gish, Gerald
AU - Pawson, Tony
AU - Haser, Wayne G.
AU - King, Fred
AU - Roberts, Tom
AU - Ratnofsky, Sheldon
AU - Lechleider, Robert J.
AU - Neel, Benjamin G.
AU - Birge, Raymond B.
AU - Fajardo, J. Eduardo
AU - Chou, Margaret M.
AU - Hanafusa, Hidesaburo
AU - Schaffhausen, Brian
AU - Cantley, Lewis C.
N1 - Funding Information:
The original modeling of the pTyr-Glu-Glu-lie phosphopeptide in the Src SH2 domain was done by John Kuriyan (Rockefeller University). We thank Dr. Kuriyan for sharing his crystal coordinates and for many informative discussions about modeling. We also thank Stephen Harrison (Harvard University) for discussion about the Lck SH2 domain. We thank Michael Berne (Tufts University School of Medicine, Boston, MA) for microsequencing and for synthesizing some of the phospho-peptides. We thank Bill Bachovchin and David Sanford (Tufts University School of Medicine) for nuclear magnetic resonance analysis to confirm the pTyr and 0-methoxyphosphotyrosine content of the phos-phopeptides and for modeling of the ~85 N-terminal SH2 domain. This work was supported by grants from the National Institutes of Health and funds from the BASF corporation.
PY - 1993/3/12
Y1 - 1993/3/12
N2 - 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.
AB - 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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U2 - 10.1016/0092-8674(93)90404-E
DO - 10.1016/0092-8674(93)90404-E
M3 - Article
C2 - 7680959
AN - SCOPUS:0027403027
SN - 0092-8674
VL - 72
SP - 767
EP - 778
JO - Cell
JF - Cell
IS - 5
ER -