ABSTRACT
From the classic studies on glycogen metabolism by the Coris and their co-workers came the discovery that protein phosphorylation plays an important role in metabolic regulation. Their initial observations paved the way to the discovery of phosphorylase kinase and to the eventual discovery of cyclic adenosine 3',5'-monophosphate by Sutherland. Most protein kinases that are classified in these latter two categories transfer phosphate from Magnesium adenosine 5'-triphosphate to tyrosine instead of to the more frequently observed phosphate acceptors serine and threonine. The protein kinases appear to have been assembled as modular structures, presumably by a mechanism involving exon shuffling. The only module that is common to all and shares extensive sequence similarities is the one corresponding to the catalytic unit. These modules frequently contain a ligand binding site which, when occupied by the appropriate ligand, triggers conformational changes leading to activation of catalytic activity.
