Molecular regulation of the HKalpha2 subunit of the H+,K(+)-ATPases.

H+, K(+)-Adenosine triphosphatases (H+, K(+)-ATPase) located in the mammalian kidney participate in maintaining ion and acid/base balance. The molecular mechanisms by which physiological conditions lead to an upregulation of H+, K(+)-ATPase activity are poorly understood. However, studies in recent years have provided tangible progress towards understanding the role of the renal H+, K(+)-ATPases. The cloning of cDNAs from the kidneys of several mammalian species has provided evidence for the presence of several H+, K(+)-ATPase isoforms. The different H+, K(+)-ATPases may make distinct contributions to ion and acid/base balance. Studies of mRNA, protein and H+, K(+)ATPase activity levels in the kidney under a variety of physiological conditions have revealed that the HKalpha2 (colonic) subunit of the H+, K(+)ATPase is highly regulated. The pump is responsive to potassium, sodium and probably hormones. Recent developments have focused on defining the HKa2 gene promoter. Analysis of the 5' end of the HKalpha2 gene from human, rat and rabbit has identified conserved elements that may serve as core promoter and regulatory elements. This review will summarize recent data related to the molecular regulation of the HKalpha2 subunit of the H+, K(+)-ATPase.