THE STRUCTURAL BASIS FOR SUBSTRATE RECOGNITION AND CONTROL BY PROTEIN-KINASES

Protein kinases catalyse phospho transfer reactions from ATP to serine , threonine or tyrosine residues in target substrates and provide hey mechanisms for control of cellular signalling processes. The crystal s tructures of 12 protein kinases are now known, These include structure s of kinases in the active state in ternary complexes with ATP (or ana logues) and inhibitor or peptide substrates (e,g, cyclic AMP dependent protein kinase, phosphorylase kinase and insulin receptor tyrosine ki nase); kinases in both active and inactive states (e,g, CDK2/cyclin A, insulin receptor tyrosine kinase and MAPK); kinases in the active sta te (e,g, casein kinase 1, Lck); and kinases in inactive states (e.g, t witchin kinase, calcium calmodulin kinase 1, FGF receptor kinase, c-Sr c and Hck), This paper summarises the detailed information obtained,vi th active phosphorylase kinase ternary complex and reviews the results with reference to other kinase structures for insights into mechanism s for substrate recognition and control, (C) 1998 Federation of Europe an Biochemical Societies.