Modulation of H,K-ATPase activity by the molecular chaperone ERp57 highly expressed in gastric parietal cells

ERp57 is a ubiquitous ER chaperone that has disulfide isomerase activity. Here, we found that both ERp57 and gastric H⁺,K⁺-ATPase are expressed in a sample derived from the apical canalicular membranes of parietal cells. Overexpression of ERp57 in HEK293 cells stably expressing H⁺,K⁺-ATPase significantly increased the ATPase activity without changing the expression level of H⁺,K⁺-ATPase. Interestingly, overexpression of a catalytically inactive mutant of ERp57 (C57S/C60S/C406S/C409S) in the cells also increased H⁺,K⁺-ATPase activity. In contrast, knockdown of endogenous ERp57 in H⁺,K⁺-ATPase-expressing cells significantly decreased ATPase activity without changing the expression level of H⁺,K⁺-ATPase. Overexpression and knockdown of ERp57 had no significant effect on the expression and function of Na⁺,K⁺-ATPase. These results suggest that ERp57 positively regulates H⁺,K⁺-ATPase activity apart from its chaperoning function.