Adenylate cyclase-coupled vasopressin receptor activates AQP2 promoter via a dual effect on CRE and AP1 elements.
Vasopressin plays an essential role for the regulation of water balance by activating the collecting duct-specific water channel, aquaporin-2 (AQP2). Here we present evidence that vasopressin may also act as a long-term, transcriptional regulator of AQP2. The studies were performed on LLC-PK1 cells, which normally express V2 receptor (V2R) and which were transfected with a fragment of the human AQP2 promoter. Activation of the adenylate cyclase-coupled V2R in LLC-PK1 cells induced phosphorylation of adenosine 3',5'-cyclic monophosphate (cAMP) responsive element binding protein (CREB) and expression of c-Fos. Binding of these factors to the CRE and AP1 site did, in combination, lead to AQP2 promoter activation. These results establish the role of vasopressin as a regulator of transcription and are the first example of how a message from a highly specific receptor is, via a dual effect of the cAMP signal on CREB and immediate early gene expression, transduced to the transcription of a final target protein with known biological effects.
Yasui
M
M
Department of Woman and Child Health, Pediatric Unit, St. Goran's Children's Hospital, Karolinska Institute, Stockholm, Sweden.
Zelenin
S M
SM
Celsi
G
G
Aperia
A
A
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D001665:Binding Sites; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D007473:Ion Channels / Q000096:biosynthesis / Q000235:genetics*; D007700:Kinetics; D008954:Models, Biological; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D017483:Receptors, Vasopressin / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014162:Transfection; D014667:Vasopressins / Q000494:pharmacology*
C496023:AQP2 protein, human; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D017362:Cyclic AMP Response Element-Binding Protein; D007473:Ion Channels; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D017483:Receptors, Vasopressin; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; D014667:Vasopressins; D015240:Phorbol 12,13-Dibutyrate; D000242:Cyclic AMP; D015500:Chloramphenicol O-Acetyltransferase; D000262:Adenylyl Cyclases; D003894:Deamino Arginine Vasopressin