The Albert Lasker Medical Awards. Role of the cyclic AMP-dependent protein kinase in signal transduction

Abstract

The first example of an enzyme that undergoes phosphorylation and dephosphorylation was phosphorylase, which catalyzes the initial step in the breakdown of tissue glycogen, a process that occurs when cells are stimulated by certain hormones. The phosphorylation reaction that activates phosphorylase is catalyzed by an enzyme designated "phosphorylase kinase," whereas the dephosphorylation reaction is catalyzed by an enzyme called "phosphorylase phosphatase." Phosphorylase kinase, like phosphorylase itself, is regulated by phosphorylation-dephosphorylation. In this instance the enzyme is phosphorylated and activated by a protein kinase that is the intracellular target of adenosine 3',5'-cyclic phosphate, the second messenger of hormone action that was discovered by the late Earl Sutherland. Knowledge of these steps led to the establishment of the glycogenolytic cascade in which adenosine 3',5'-cyclic phosphate, formed as a result of hormone action, first activates the adenosine 3',5'-cyclic phosphate-dependent protein kinase, which in turn activates phosphorylase kinase, which then converts inactive phosphorylase to its active form. This is followed by the breakdown of glycogen.