THE INTERRELATIONSHIP BETWEEN CAMP-DEPENDENT ALPHA-SUBUNIT AND BETA-SUBUNIT PHOSPHORYLATION IN THE REGULATION OF PHOSPHORYLASE-KINASE ACTIVITY - STUDIES USING SUBUNIT SPECIFIC PHOSPHATASES

  • 5 March 1987
    • journal article
    • research article
    • Vol. 262  (7) , 3210-3218
Abstract
This study addresses the function of multisite phosphorylation of phosphorylase kinase catalyzed by the cAMP-dependent protein kinase. Using subunit specific protein phosphatases (the polycation-stimulated and ATP-, Mg2+-dependent enzymes), we show that the degree of phosphorylation of both the .alpha. and .beta. subunits modulates phosphorylase kinase activity. .beta. subunit phosphorylation is essential for activation and, independent of the degree of .alpha. subunit phosphorylation, enzyme fully dephosphorylated in the .beta. subunit is completely inactivated. .alpha. Subunit phosphorylation does, however, also regulate activity, and enzyme fully or partially phosphorylated in the .beta. subunit is inactivated as a consequence of .alpha. subunit dephosphorylation. The extent of inactivation caused by .alpha. subunit dephosphorylation is linearly dependent on the phosphorylation state of the .beta. subunit. Three peptide sites on the .alpha. subunit are phosphorylated by the cAMP-dependent protein kinase; the site primarily affecting activity is the one that is initially phosphorylated. These data provide evidence that subunit interrelationships play an important role in the regulation of phosphorylase kinase by multisite phosphorylation.