INSIGHTS INTO SRC KINASE FUNCTIONS - STRUCTURAL COMPARISONS

Recent structures of Src tyrosine kinases reveal complex mechanisms fo r regulation of enzymatic activity. The regulatory SH3 and SH2 domains bind to the back of the catalytic kinase domain via a linker region t hat joins the SH2 domain to the catalytic domain. Members of a subgrou p of the Src kinase family show distinct features in this linker and i n the loops that interact with it. Hydrophobicity of key residues in t his region is important for intramolecular regulation. The kinases Abl , Btk and Csk seem to have the same molecular architecture as Src, Str uctural comparisons between serine/threonine and tyrosine kinases indi cate a specific twisting mechanism involving the N- and C-terminal lob es of the catalytic domain. This motion could provide insights into th e various mechanisms used to regulate kinase activity.