RENAL EXPRESSION OF THE GENE ENCODING THE GASTRIC H+-K+-ATPASE BETA-SUBUNIT

The gastric mucosal parietal cells and cells of the renal collecting duct both possess H+-K+-adenosinetriphosphatase (H+-K+-ATPase) activities. In the stomach, the H+-K+-ATPase (EC 3.6.1.3) is responsible for acidification of luminal contents. The kidney H+-K+-ATPase protein(s) contribute to potassium reabsorption and secretion of hydrogen ions to maintain potassium and acid-base homeostasis. The stomach H+-K+-ATPase is well defined and consists of an alpha-catalytic subunit of apparent molecular mass of 95 kDa and a highly glycosylated beta-subunit of 60-90 kDa. The molecular identity of the protein that mediates the H+-K+-ATPase activity in the kidney has been addressed in this paper. A combination of RNA hybridizations, polymerase chain reaction analysis of kidney RNA, and sequence analysis of cDNAs indicated that gastric H+-K+-ATPase beta-subunit mRNA is present in kidney. Immunoblotting with antibodies specific for the gastric H+-K+-ATPase beta-subunit detected proteins, which, after deglycosylation, had the same molecular mass as the gastric beta-subunit in membrane protein preparations from rabbit, pig, rat, and mouse kidneys. Furthermore, we have used transgenic mice to demonstrate that the gastric H+-K+-ATPase beta-subunit gene contains cis-acting regulatory sequences that are active in both gastric parietal cells and the renal collecting ducts. Overall, these data indicate that the gastric H+-K+-ATPase beta-subunit is found in the kidney and probably associates with the gastric H+-K+-ATPase alpha-subunit and/or other P-type ATPase alpha-subunits, thus contributing to acid-base and potassium homeostasis.