RT Journal Article
SR Electronic
T1 The N Terminus Domain of Type VI Adenylyl Cyclase Mediates Its Inhibition by Protein Kinase C
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 644
OP 650
DO 10.1124/mol.56.3.644
VO 56
IS 3
A1 Hsing-Lin Lai
A1 Ting-Hui Lin
A1 Yu-Ya Kao
A1 Wu-Ja Lin
A1 Ming-Jing Hwang
A1 Yijuang Chern
YR 1999
UL http://molpharm.aspetjournals.org/content/56/3/644.abstract
AB 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 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 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, Ser10 was found to serve as an acceptor for the PKC-mediated phosphorylating transfer of ACVI.