Conformation-dependent activation of type II adenylyl cyclase by protein kinase C.
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.
Ebina
T
T
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Kawabe
J
J
Katada
T
T
Ohno
S
S
Homcy
C J
CJ
Ishikawa
Y
Y
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
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