Control of a novel adenylyl cyclase by calcineurin.
The molecular complex formed by the immunosuppressant FK506 and the immunophilin protein FKBP12 potently inhibits the Ca2+/calmodulin-activated protein phosphatase calcineurin. This mechanism appears to be common to all types of cell, implying that fundamental physiological modes of calcineurin regulation are exploited by immunosuppressants. The present paper describes a novel adenylyl cyclase regulated by calcineurin that contains an FKBP12-like domain and may thus constitute a physiologically relevant calcineurin docking site mimicked by immunosuppressant-immunophilin complexes. The enzyme messenger RNA is particularly enriched in the cerebral cortex, striatum and hippocampus, where it is localized to neuronal perikarya, indicative of an important role in neuronal function.
Paterson
J M
JM
MRC Brain Metabolism Unit, University of Edinburgh, Scotland, UK.
Smith
S M
SM
Harmar
A J
AJ
Antoni
F A
FA
D000262:Adenylyl Cyclases / Q000096:biosynthesis*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000201:enzymology; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D003342:Corpus Striatum / Q000201:enzymology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007668:Kidney; D008322:Mammals; D051379:Mice; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D018019:Receptors, Corticotropin-Releasing Hormone / Q000096:biosynthesis / Q000502:physiology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D016559:Tacrolimus / Q000494:pharmacology; D022021:Tacrolimus Binding Proteins; D014162:Transfection
D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D011994:Recombinant Proteins; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D000262:Adenylyl Cyclases; D022021:Tacrolimus Binding Proteins; D016559:Tacrolimus