Synergistic activation of insect cAMP-dependent protein kinase A (type II) by cyclicAMP and cyclicGMP

The high cGMP sensitivity of cAMP-dependent protein kinase A (type II) (PKAII) from invertebrates led to the hypothesis that cGMP directly activates PKAII under physiological conditions. We tested this idea using PKAII holoenzyme purified from the honeybee brain in an assay with short stimulation times. In the presence of very low cAMP concentrations, we found a synergistic increase in PKAII activation by physiological cGMP concentrations. Cloning honeybee regulatory subunit RII and phylogenetic comparison of the two cyclic nucleotide-binding sites of RII reveal a high relation of domain A of insect RII with cGMP-binding domains of cGMP-dependent protein kinases.