Cyclic AMP-Dependent Protein Phosphorylation

Since the early findings that most if not all effects of cAMP are mediated via its binding to the regulatory subunit of cAMP-dependent protein kinase, a considerable amount of effort has been expended delineating the mechanism(s) by which cAMP activates protein kinase and what the functions of the active kinase are in the cell. Some of the more important general observations can be summarized as follows. Two major types of cAMP-dependent protein kinase are known; both types exist as asymetric tetramers composed of two catalytic subunits (C) and one dimeric regulatory subunit (R2). Upon exposure to a saturating dose of cAMP a three species complex of cAMP, regulatory and catalytic subunit is formed. At what are probably physiological concentrations of enzyme, this complex dissociates into two free, active catalytic subunits and one R dimer having 4 cyclic AMP molecules bound. The Kd of the R: C interaction for either major isozyme type appears to be about 0.5 nM. The association and dissociation rates are probably fast enough at physiological enzyme concentrations to allow protein kinase to mediate rapidly oscillating processes in vivo.