title: Isoform-dependent activation of adenylyl cyclase by proteolysis.
abstract: Recent findings have suggested that the cellular proteolytic system plays a major role in the regulation of various intra- and extra-cellular signaling. It was previously shown that proteolytic treatment of adenylyl cyclase leads to the activation of this enzyme. We demonstrate that this activation occurs in an adenylyl cyclase isoform-dependent manner. The type II isoform was strongly activated (approximately 500%), the type III isoform was modestly activated (approximately 30%),and the type V isoform was inhibited by trypsin. Activation of type II adenylyl cyclase occurred in trypsin dose- and time-dependent manners and was blocked by a trypsin inhibitor in a dose-dependent manner. Other proteases, such as thrombin and plasminogen, similarly activated the type II isoform, but not the others. Our data suggest that proteolytic activation is an isoform- and thus cell type-dependent mechanism of altering adenylyl cyclase catalytic activity.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: T
authors.initials: T
authors.lastname: Ebina
authors.forename: Y
authors.initials: Y
authors.lastname: Toya
authors.forename: N
authors.initials: N
authors.lastname: Oka
authors.forename: J
authors.initials: J
authors.lastname: Kawabe
authors.forename: C
authors.initials: C
authors.lastname: Schwencke
authors.forename: Y
authors.initials: Y
authors.lastname: Ishikawa
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D010450:Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation; D005341:Fibrinolysin / Q000494:pharmacology; D007313:Insecta; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D010059:Ovomucin / Q000494:pharmacology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D014357:Trypsin / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000494:pharmacology
chemical_list: D007527:Isoenzymes; D011994:Recombinant Proteins; D014361:Trypsin Inhibitors; D010059:Ovomucin; D010450:Endopeptidases; D014357:Trypsin; D013917:Thrombin; D005341:Fibrinolysin; D000262:Adenylyl Cyclases