Cloning of the human TASK-2 (KCNK5) promoter and its regulation by chronic hypoxia.
The tandem P domain potassium channel family includes five members of the acid-sensing subfamily, TASK. TASK channels are active at resting potential and are inhibited by extracellular protons, suggesting they function as acid sensors and control excitability/ion homeostasis. Indeed, TASK-2 (KCNK5) has been shown to control excitability, volume regulation, bicarbonate handling, and apoptosis in a variety of tissues. With such diverse functions being ascribed to TASK-2, it is important to understand long-term as well as short-term regulation of this important channel. Thus, we have cloned the TASK-2 promoter, demonstrated that its transcriptional activity is dependent upon pO(2), shown that deletion of overlapping consensus binding sites for NF-kappaB/Elk-1 ablates this O(2) sensitivity, and proved that Elk-1 binds preferentially to this site. Furthermore, the consequences of chronic hypoxia on natively expressed TASK-2 are decreased steady-state mRNA and cell depolarization showing that TASK-2 contributes to the excitability of this important lung cell type.
Brazier
Stephen P
SP
School of Biosciences, Museum Avenue, Cardiff University, UK.
Mason
Helen S
HS
Bateson
Alan N
AN
Kemp
Paul J
PJ
D001483:Base Sequence; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D015536:Down-Regulation; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
C410295:KCNK5 protein, human; D016328:NF-kappa B; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger; D010100:Oxygen