The phosphorylation status of membrane-bound nucleoside diphosphate kinase in epithelia and the role of AMP: Mol Cell Biochem

Kate J. Treharne, Oliver Giles Best, Anil Mehta

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Nucleoside diphosphate kinase (NDPK) has many roles and is present in different locations in the cell. Membrane-bound NDPK is present in epithelial fractions enriched for the apical membrane. Here, we show in human, mouse and sheep airway membranes, that the phosphorylation state of membrane-bound NDPK on histidine and serine residues differs dependent on many regulatory factors. GTP (but not ATP) promotes serine phosphorylation (pSer) of NDPK. Further we find that rising [AMP] promotes pSer (only with GTP) but inhibits histidine phosphorylation (pHis) of NDPK from both donors. We find that NDPK co-immunoprecipitates reciprocally with AMP-activated kinase and that these two proteins can co-localise in human airways. AMP concentrations rise rapidly when ATP is depleted or during hypoxia. We find that, in human airway cells exposed to hypoxia (3% oxygen), membrane-bound NDPK is inhibited. Although histidine phosphorylation should in principle be independent of the nucleotide triphosphates used, we speculate that this membrane pool of NDPK may be able to switch function dependent on nucleotide species.
Original languageEnglish
Pages (from-to)107-114
Number of pages8
JournalMOLECULAR AND CELLULAR BIOCHEMISTRY
Volume329
Issue number1-2
DOIs
Publication statusPublished - Sep 2009
Externally publishedYes

Keywords

  • AMP-Activated Protein Kinases
  • pharmacology
  • metabolism Uridine Monophosphate
  • enzymology
  • drug effects Sheep Trachea
  • metabolism Phosphorylation
  • metabolism Mice Molecular Weight Nucleoside-Diphosphate Kinase
  • chemistry
  • pharmacology Humans Membrane Proteins
  • metabolism Guanosine Monophosphate
  • metabolism Epithelium
  • Cultured Epithelial Cells
  • metabolism Cells
  • cytology Cell Membrane
  • pharmacology Animals Bronchi
  • metabolism Adenosine Monophosphate

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