Catalytic specificity of protein-tyrosine kinases is critical for selective signalling

摘要: HOW do distinct protein-tyrosine kinases activate specific downstream events? Src-homology-2 (SH2) domains on tyrosine or targets of recognize phosphotyrosine in a sequence context and thereby provide some specificity1–3. The role the catalytic site determining target specificity has not been fully investigated. Here we use degenerate peptide library to show that each nine investigated unique optimal substrate. We find cytosolic preferentially phosphorylate peptides recognized by their own SH2 closely related (group I; ref. 3), whereas receptor subsets group III domains3. importance these findings for human disease is underscored our observation point mutation RET receptor-type kinase, which causes multiple endocrine neoplasia type 2B, results shift substrate specificity.