Vol. 156, No. 2, 1988 October 31, 1988 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Pages 801-806 DIFFERENTIAL SENSITIVITY OF NEURAL AND NON-NEURAL PROTEIN KINASE ISOZYMES TO CYCLIC AMP Deepak Bhatnagar*, Andrew A. Burton, and Robert Roskoski, Jr. Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, Ii00 Florida Avenue, New Orleans, Louisiana 70119 Received August 27, 1988 SUMMARY - Cyclic AMP-dependent protein kinase, which plays a major role in metabolic and genetic regulation, consists of two classes of isozymes denoted as type I and type II. The type II isozyme, moreover, consists of two subclasses denoted as neural and non-neural based upon in~nunechemical differences between the enzyme isolated from bovine brain and heart, respectively. Whereas the catalytic (C) subunits of these three isozymes are quite similar, all three isozymes differ with respect to their regulatory (R) subunits. In the present report, we have conloared the sensitivities to cyclic AMP of the type I and type II isozymes in several tissues from a single species (rat). The sensitivities of the three isozymes to cyclic AMP were type I >> non-neural type II > neural type II. We suggest that the differences in sensitivity to cyclic AMP of isozymes present in the same cell provides the cell with a dynamic range of responses to the widely varying alterations in cellular cyclic AMP levels produced by regulatory first messengers. Cyclic AMP-dependent protein kinase exists as an inactive tetrameric holoenzyme (R2C2) made up of two regulatory (R) and two catalytic (C) subunits. In general, each R subunit binds two molecules of cyclic AMP which leads to dissociation of the holoenzyme and activation of phosphotransferase activity (i). Because the binding of cyclic AMP to the R subunits exhibits positive cooperativity (2), the range of cyclic AMP within which the activity of a particular protein kinase is regulated is limited. The type II R subunit from bovine brain, which differs ir~nunochemically from that of non-neural tissues (37, may bind only one cyclic AMP (4) and may not exhibit cooperativity. Following dissociation, the C subunit then catalyzes the phosphorylation of target proteins on sequence specific serine (or threonine) residues. *Author to whom correspondence should be addressed and present address Southern Regional Research Center, USDA/ARS, ii00 Robert E. Lee Blvd., P.O. Box 19687, New Orleans, Louisiana 70179 0006-291X/88 $1.50 801