The N Terminus Domain of Type VI Adenylyl Cyclase Mediates Its Inhibition by Protein Kinase C

Previous results from our laboratory have shown that phos-phorylation of type VI adenylyl cyclase (ACVI) by protein kinase C (PKC) caused suppression of adenylyl cyclase activity. In the present study, we investigated the role of the N terminus cyto-solic domain of ACVI in this PKC-mediated inhibition of ACVI. Removal of amino acids 1 to 86 of ACVI or mutation of Ser10 (a potential PKC phosphorylation site) into alanine significantly relieved the PKC-mediated inhibition and markedly reduced the PKC-evoked protein phosphorylation. PKC also effectively phosphorylated a recombinant N terminus cytosolic domain (amino acids 1–160) protein of ACVI and a synthetic peptide representing Ser10. In addition, the amino acids 1 to 86 trun-cated mutant exhibited kinetic properties similar to those of the wild type. Taken together, these data demonstrate that th