Identification of a novel protein kinase A anchoring protein that binds both type I and type II regulatory subunits

Compartmentalization of cAMP-dependent protein kinase is achieved in part by interaction with A-kinase anchoring proteins (AKAPs), All of the anchoring proteins identified previously target the kinase by tethering the type II regulatory subunit, Here we report the cloning and characterization of a novel anchoring protein, D-AKAP1, that interacts with the N terminus of both type I and type II regulatory subunits, A novel cDNA encoding a 125-amino acid fragment of D-AKAP1 was isolated from a two-hybrid screen and shown to interact specifically with the type I regulatory subunit, Although a single message of 3.8 kilobase pairs was detected for D-AKAP1 in all embryonic stages and in most adult tissues, cDNA cloning revealed the possibility of at least four splice variants, All four isoforms contain a core of 526 amino acids, which includes the R binding fragment, and may be expressed in a tissue-specific manner, This core sequence was homologous to S-AKAP84, including a mitochondrial signal sequence near the amino terminus (Lin, R, Y., Moss, S, B,, and Rubin, C, S, (1995) J, Biol, Chem. 270, 27804-27811), D-AKAP1 and the type I regulatory subunit appeared to have overlapping expression patterns in muscle and olfactory epithelium by in situ hybridization, These results raise a novel possibility that the type I regulatory subunit may be anchored via anchoring proteins.