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Gauging the signaling space of the Src homology 2 domain by peptide and protein arrays
Author(s) -
Li Shawn S,
Huang Haiming,
Wu Chenggang,
Li Lei
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.310
Subject(s) - sh2 domain , peptide , proto oncogene tyrosine protein kinase src , computational biology , chemistry , peptide library , homology (biology) , biology , biochemistry , signal transduction , peptide sequence , amino acid , gene
Different SH2 domains select for distinct phosphopeptides, and deciphering the peptide motif recognized by an SH2 domain and identifying the interactions mediated by the domain is the key to understanding its function. We have determined the phosphotyrosyl peptide‐binding properties of 76 SH2 domains by screening an oriented peptide array library (OPAL). A number of novel binding motifs have been identified, which is exemplified by the BRDG1SH2 domain that selects specifically for a bulky, hydrophobic residue at the +4 position relative to the pTyr residue. Based on the OPAL binding patterns, we developed SMALI a web‐based program for predicting binding partners for SH2‐containing proteins. When applied to SH2D1A/SAP, a protein whose mutation or deletion underlies the X‐linked lymphoproliferative syndrome, SMALI not only recapitulated known interactions but also identified a number of novel binding partners for this disease‐associated protein. By combining SMALI prediction with peptide array‐target screening (PATS), we identified a signaling network mediated by a group of SH2 domains that provides a framework upon which the functions of SH2 domains can be systematically explored.