ABSTRACT

Cyclic AMP-dependent protein kinase (PK-A) phosphorylates many proteins. Although the substrates show little apparent similarity, they obviously must have some structure in common which is recognized by the active site of PK-A. Although a considerable number of proteins are phosphorylated by PK-A, they are few in comparison with the total number of intracellular proteins. This indicates a rather high substrate specificity of the protein kinase and is further emphasized by the fact that only one or a few serine or threonine residues in each substrate polypeptide chain are phosphorylated by PK-A. Substrate specificity rules for PK-A have been defined by use of synthetic peptides representing the phosphorylatable site of liver pyruvate kinase in particular, but also that of the β-subunit of phosphorylase kinase. The specificity rules established so far merit their use in the search for additional substrates of PK-A with the help of current protein sequence data bases.