title: The language of SH2 domain interactions defines phosphotyrosine-mediated signal transduction.
abstract: Natural languages arise in an unpremeditated fashion resulting in words and syntax as individual units of information content that combine in a manner that is both complex and contextual, yet intuitive to a native reader. In an analogous manner, protein interaction domains such as the Src Homology 2 (SH2) domain recognize and "read" the information contained within their cognate peptide ligands to determine highly selective protein-protein interactions that underpin much of cellular signal transduction. Herein, we discuss how contextual sequence information, which combines the use of permissive and non-permissive residues within a parent motif, is a defining feature of selective interactions across SH2 domains. Within a system that reads phosphotyrosine modifications this provides crucial information to distinguish preferred interactions. This review provides a structural and biochemical overview of SH2 domain binding to phosphotyrosine-containing peptide motifs and discusses how the diverse set of SH2 domains is able to differentiate phosphotyrosine ligands.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, Ontario, Canada M5G 1X5.
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Liu
authors.forename: Brett W
authors.initials: BW
authors.lastname: Engelmann
authors.forename: Piers D
authors.initials: PD
authors.lastname: Nash
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010748:Phosphopeptides / Q000737:chemistry; D019000:Phosphotyrosine / Q000737:chemistry*; D010802:Phylogeny; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D018909:src Homology Domains
chemical_list: D010748:Phosphopeptides; D019000:Phosphotyrosine