title: Protein phosphatase 2A interacts with the Na,K-ATPase and modulates its trafficking by inhibition of its association with arrestin.
abstract: BACKGROUND
  The P-type ATPase family constitutes a collection of ion pumps that form phosphorylated intermediates during ion transport. One of the best known members of this family is the Na⁺,K⁺-ATPase. The catalytic subunit of the Na⁺,K⁺-ATPase includes several functional domains that determine its enzymatic and trafficking properties.
  
  
  RESULTS
  Using the yeast two-hybrid system we found that protein phosphatase 2A (PP2A) catalytic C-subunit is a specific Na⁺,K⁺-ATPase interacting protein. PP-2A C-subunit interacted with the Na⁺,K⁺-ATPase, but not with the homologous sequences of the H⁺,K⁺-ATPase. We confirmed that the Na⁺,K⁺-ATPase interacts with a complex of A- and C-subunits in native rat kidney. Arrestins and G-protein coupled receptor kinases (GRKs) are important regulators of G-protein coupled receptor (GPCR) signaling, and they also regulate Na⁺,K⁺-ATPase trafficking through direct association. PP2A inhibits association between the Na⁺,K⁺-ATPase and arrestin, and diminishes the effect of arrestin on Na⁺,K⁺-ATPase trafficking. GRK phosphorylates the Na⁺,K⁺-ATPase and PP2A can at least partially reverse this phosphorylation.
  
  
  CONCLUSIONS
  Taken together, these data demonstrate that the sodium pump belongs to a growing list of ion transport proteins that are regulated through direct interactions with the catalytic subunit of a protein phosphatase.
authors.affiliation: Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kimura
authors.forename: Wonsun
authors.initials: W
authors.lastname: Han
authors.forename: Philipp
authors.initials: P
authors.lastname: Pagel
authors.forename: Angus C
authors.initials: AC
authors.lastname: Nairn
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Caplan
mesh_terms: D000818:Animals; D019393:Arrestin / Q000378:metabolism*; D001667:Binding, Competitive; D019556:COS Cells; D002522:Chlorocebus aethiops; D054768:G-Protein-Coupled Receptor Kinases / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D047468:Immunoprecipitation; D007668:Kidney / Q000201:enzymology; D051379:Mice; D010766:Phosphorylation; D011485:Protein Binding; D014176:Protein Biosynthesis; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D019393:Arrestin; D021122:Protein Subunits; D054768:G-Protein-Coupled Receptor Kinases; D054648:Protein Phosphatase 2; D000254:Sodium-Potassium-Exchanging ATPase