Ca2(+)-dependent proteolytic modification of the cAMP-dependent protein kinase in Drosophila wild-type and dunce memory mutants.

Two cAMP-dependent protein kinases with different activation constants were separated from Drosophila melanogaster head extracts. Both are only found in nervous tissue. The first cAMP-dependent kinase, with Mr = 190,000, has been already characterized as tetrameric Drosophila type II cAMP-dependent protein kinase R2C2. The second purified cAMP-dependent protein kinase, with Mr = 80,000, is dimeric in structure RPC, and the cAMP-concentration required for half maximal activation is 4 fold lower than for the type II kinase. The generation of RP can be stimulated in vitro by addition of exogenous calcium and is due to an endogenous Ca2(+)-dependent protease that selectively degrades the regulatory subunit. Extraction in the presence of various protease inhibitors does not affect the amounts of RP, suggesting that the observed quantitative change in RP occurs in vivo. The amounts of RP in the nervous tissue of the memory mutants dunce1 and dunce2, which have increased cAMP levels, are different from the amount of RP in wild-type flies. Also treatments of wild-type flies with drugs affecting cAMP-metabolism and acetylcholine levels led to amounts of RP different from untreated flies.