Na+ and K+ regulate the phosphorylation state of nucleoside diphosphate kinase in human airway epithelium.
We describe how cations, in the presence of ATP, regulate the phosphorylated form of 19- and 21-kDa nucleoside diphosphate kinase (NDPK; EC 2.7.4.6), a kinase controlling K+ channels, G proteins, cell secretion, cellular energy production, and UTP synthesis. In apically enriched human nasal epithelial membranes, 10 mM Na+ inhibits phosphorylation of NDPK relative to other cations. Dose response showed that, whereas K+ induces a fourfold greater phosphate incorporation (EC50 10 mM), Na+ is inhibitory (EC50 10 mM) compared with respective buffer controls. Cation discrimination is nucleotide selective (not seen with [gamma-32P]GTP) and NDPK specific (not seen with p37h, a previously characterized Cl--sensitive phosphoprotein). Na+ does not exert an inhibitory effect on NDPK phosphorylation directly but is likely to act via an okadaic acid-insensitive phosphatase. We speculate that the ability of NDPK to discriminate between physiologically relevant cation concentrations provides a novel example of cross talk within the apical membrane.
Marshall
L J
LJ
Department of Child Health, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, United Kingdom.
Muimo
R
R
Riemen
C E
CE
Mehta
A
A
D000255:Adenosine Triphosphate / Q000502:physiology; D000328:Adult; D002021:Buffers; D002412:Cations / Q000494:pharmacology; D003080:Cold Temperature; D006160:Guanosine Triphosphate / Q000502:physiology; D006801:Humans; D008970:Molecular Weight; D009297:Nasal Mucosa / Q000166:cytology / Q000378:metabolism*; D009701:Nucleoside-Diphosphate Kinase / Q000737:chemistry / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology / Q000502:physiology*; D012964:Sodium / Q000494:pharmacology / Q000502:physiology*
D002021:Buffers; D002412:Cations; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D012964:Sodium; D009701:Nucleoside-Diphosphate Kinase; D010744:Phosphoric Monoester Hydrolases; D011188:Potassium