title: Nongastric H,K-ATPase: structure and functional properties.
abstract: Nongastric H,K-ATPases whose catalytic subunits (AL1) encoded by human ATP1AL1 and homologous animal genes comprise the third distinct group within the X,K-ATPase family. No unique nongastric beta has been identified. Precise in situ colocalization and strong association of AL1 with beta1 of Na,K-ATPase was detected in apical membranes of rodent prostate epithelium. In this tissue, beta1NK serves as an authentic subunit of both the Na,K- and nongastric H,K-pumps. Upon expression in Xenopus oocytes the human AL1 can assemble with beta1NK, and more efficiently with gastric betaHK, into functional H,K-pumps. Both AL1/beta complexes exhibit a similar K-affinity, and their K-transport depends on intra- and extracellular Na. These data provide new evidence that nongastric H,K-ATPase can perform Na/K-exchange, and indicate that beta does not significantly affect this ion-pump function. Analysis of human nongastric H,K-ATPase expressed in Sf-21 insect cells revealed that AL1/betaHK exhibits substantial enzymatic activities in K-free medium and K stimulates, but Na has inhibitory effect on ATP hydrolysis. Thus, although the nongastric H,K-ATPase can function as Na/K exchanger, its reaction mechanism is different from that of the Na,K-ATPase. Human nongastric H,K-ATPase is highly sensitive to bufalin, digoxin, and digitoxin, but almost resistant to digoxigenin and ouabagenin.
authors.affiliation: Department of Pharmacology, Medical College of Ohio, Toledo 43614, USA. nmodyanov@mco.edu
authors.forename: Nikolai
authors.initials: N
authors.lastname: Modyanov
authors.forename: Nikolay
authors.initials: N
authors.lastname: Pestov
authors.forename: Gail
authors.initials: G
authors.lastname: Adams
authors.forename: Gilles
authors.initials: G
authors.lastname: Crambert
authors.forename: Manoranjani
authors.initials: M
authors.lastname: Tillekeratne
authors.forename: Hao
authors.initials: H
authors.lastname: Zhao
authors.forename: Tatyana
authors.initials: T
authors.lastname: Korneenko
authors.forename: Mikhail
authors.initials: M
authors.lastname: Shakhparonov
authors.forename: Käthi
authors.initials: K
authors.lastname: Geering
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D004847:Epithelial Cells / Q000201:enzymology; D017506:H(+)-K(+)-Exchanging ATPase / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007477:Ions / Q000378:metabolism; D008297:Male; D009865:Oocytes / Q000201:enzymology; D011467:Prostate / Q000166:cytology / Q000201:enzymology; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D014981:Xenopus
chemical_list: D007477:Ions; D021122:Protein Subunits; D017506:H(+)-K(+)-Exchanging ATPase