title: Modulation of H(+),K(+)-ATPase activity by the molecular chaperone ERp57 highly expressed in gastric parietal cells.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Physiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Takuto
authors.initials: T
authors.lastname: Fujii
authors.forename: Shun-Ya
authors.initials: SY
authors.lastname: Awaka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Fujita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsuji
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shimizu
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Gomi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsukada
authors.forename: Hideki
authors.initials: H
authors.lastname: Sakai
mesh_terms: D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D055785:Gene Knockdown Techniques; D017506:H(+)-K(+)-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D018832:Molecular Chaperones / Q000502:physiology; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000378:metabolism*; D019704:Protein Disulfide-Isomerases / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D013552:Swine
chemical_list: D018832:Molecular Chaperones; D034741:RNA, Small Interfering; D017506:H(+)-K(+)-Exchanging ATPase; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human
keywords: ERp57; Gastric mucosa; H(+),K(+)-ATPase; Molecular chaperone; Parietal cell