title: The N terminus domain of type VI adenylyl cyclase mediates its inhibition by protein kinase C.
abstract: Previous results from our laboratory have shown that phosphorylation 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 cytosolic domain of ACVI in this PKC-mediated inhibition of ACVI. Removal of amino acids 1 to 86 of ACVI or mutation of Ser(10) (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 Ser(10). In addition, the amino acids 1 to 86 truncated mutant exhibited kinetic properties similar to those of the wild type. Taken together, these data demonstrate that the highly variable N terminus cytoplasmic domain of ACVI is a regulatory domain with a critical role in PKC-mediated suppression, which is a hallmark of this adenylyl cyclase isozyme. In addition, Ser(10) was found to serve as an acceptor for the PKC-mediated phosphorylating transfer of ACVI.
authors.affiliation: Division of Neuroscience, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
authors.forename: H L
authors.initials: HL
authors.lastname: Lai
authors.forename: T H
authors.initials: TH
authors.lastname: Lin
authors.forename: Y Y
authors.initials: YY
authors.lastname: Kao
authors.forename: W J
authors.initials: WJ
authors.lastname: Lin
authors.forename: M J
authors.initials: MJ
authors.lastname: Hwang
authors.forename: Y
authors.initials: Y
authors.lastname: Chern
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000378:metabolism; D007313:Insecta; D009154:Mutation; D010766:Phosphorylation; D011487:Protein Conformation; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012694:Serine / Q000235:genetics
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D012694:Serine; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; C121100:adenylyl cyclase 6