Diversity and Regulation of cAMP-Dependent Protein Kinases

Reversible protein phosphorylation is a key regulatory mechanism in eukaryotic cells. Protein phosphorylation was first demonstrated to regulate the activity of glycogen phosphorylase in response to glucagon (Fischer and Krebs 1955; Sutherland and Wosilait 1955). A heat-stable factor mediating the effect of glucagon on the phosphorylation status of glycogen phosphorylase was next identified as 3’,5’-cyclic adenosine monophosphate (cAMP; Sutherland and Rall 1958), and the concept of cAMP as an intracellular second messenger to a wide range of hormones, neurotransmitters, and other signaling substances was developed (Robinson et al. 1971). The target for cAMP was purified and identified as a cAMP-regulated protein kinase (Walsh et al. 1968), termed cAMP-dependent protein kinase (cAK; EC 2.7.1.37).