PT  - JOURNAL ARTICLE
AU  - Hsing-Lin Lai
AU  - Ting-Hui Lin
AU  - Yu-Ya Kao
AU  - Wu-Ja Lin
AU  - Ming-Jing Hwang
AU  - Yijuang Chern
TI  - The N Terminus Domain of Type VI Adenylyl Cyclase Mediates Its Inhibition by Protein Kinase C
AID  - 10.1124/mol.56.3.644
DP  - 1999 Sep 01
TA  - Molecular Pharmacology
PG  - 644--650
VI  - 56
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/56/3/644.short
4100  - http://molpharm.aspetjournals.org/content/56/3/644.full
SO  - Mol Pharmacol1999 Sep 01; 56
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.