title: Conformation-dependent activation of type II adenylyl cyclase by protein kinase C.
abstract: Phorbol ester treatment enhanced the catalytic activity of type II adenylyl cyclase overexpressed in insect cells. In cells coexpressing type II adenylyl cyclase and protein kinase C-alpha, type II adenylyl cyclase catalytic activity was higher even in the absence of phorbol ester treatment; phorbol ester treatment further and markedly enhanced type II adenylyl cyclase catalytic activity. However, this enhancement, either by phorbol ester treatment or by coexpression of protein kinase C-alpha, was lost following membrane solubilization with detergents. This attenuation was unaffected by phosphatase inhibitor or salts. In contrast, membrane solubilization did not affect forskolin-stimulated type II adenylyl cyclase catalytic activity. Purified type II adenylyl cyclase was stimulated by forskolin and Gs alpha, but not by protein kinase C-alpha. Therefore, a specific mammalian protein kinase C isoenzyme can activate type II adenylyl cyclase, but the mechanism clearly differs from that underlying either Gs alpha- or forskolin-mediated stimulation.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: T
authors.initials: T
authors.lastname: Ebina
authors.forename: J
authors.initials: J
authors.lastname: Kawabe
authors.forename: T
authors.initials: T
authors.lastname: Katada
authors.forename: S
authors.initials: S
authors.lastname: Ohno
authors.forename: C J
authors.initials: CJ
authors.lastname: Homcy
authors.forename: Y
authors.initials: Y
authors.lastname: Ishikawa
mesh_terms: D000262:Adenylyl Cyclases / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D015151:Immunoblotting; D019476:Insect Proteins / Q000378:metabolism; D007313:Insecta; D007527:Isoenzymes / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D015398:Signal Transduction; D013329:Structure-Activity Relationship
chemical_list: D019476:Insect Proteins; D007527:Isoenzymes; D010703:Phorbol Esters; D011092:Polyethylene Glycols; C005092:lubrol; D000242:Cyclic AMP; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D000262:Adenylyl Cyclases