Role of single turnover phosphorylation in the regulation of PKA signaling.

<p>Type II holoenzymes of PKA are under an additional feedback regulation that is mediated by the phosphorylation of the R-subunits. Holoenzyme formation creates a single turnover condition in which the catalytic subunit phosphorylates the R-subunit. Increased cAMP levels dissociate the holoenzyme as the R-subunit binds cAMP or at least unleashes the inhibitor site from the active site cleft of the C-subunit. Reassociation of the inactive holoenzyme requires the concerted action of phosphodiesterases that hydrolyse cAMP and phosphatases that remove the phosphoryl group from the inhibitor site of RIIβ. A phosphorylated yet cAMP-free RIIβ is unable to bind efficiently to the catalytic subunit. This therefore creates a self-regulating cycle that contributes to the regulation of PKA signaling. Whether the R- and C-subunits fully dissociate under these single turnover conditions is not clear, but full dissociation is not necessary. The only necessary requirement for activation is that the inhibitor site of the RIIβ subunit be released, allowing access of the nearby tail of a channel or receptor.