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Stimulation of renal Na+ dicarboxylate cotransporter 1 by Na+/H+ exchanger regulating factor 2, serum and glucocorticoid inducible kinase isoforms, and protein kinase B.

Abstract
Renal tubular citrate transport is accomplished by electrogenic Na(+) coupled dicarboxylate transporter NaDC-1, a carrier subjected to regulation by acidosis. Trafficking of the Na(+)/H(+) exchanger NHE3 is controlled by NHE regulating factors NHERF-1 and NHERF-2 and the serum and glucocorticoid inducible kinase SGK1. To test for a possible involvement in NaDC-1 regulation, mRNA encoding NaDC-1 was injected into Xenopus oocytes with or without cRNA encoding NHERF-1, NHERF-2, SGK1, SGK2, SGK3, and/or the constitutively active form of the related protein kinase B ((T308,S473D)PKB). Succinate induced inward currents (I(succ)) were taken as a measure of transport rate. Coexpression of neither NHERF-1 nor NHERF-2 in NaDC-1 expressing oocytes significantly altered I(succ). On the other hand, coexpression of SGK1, SGK3, and (T308,S473D)PKB stimulated I(succ), an effect further stimulated by additional coexpression of NHERF-2 but not of NHERF-1. The action of the kinases and NHERF-2 may link urinary citrate excretion to proximal tubular H(+) secretion.
AuthorsChristoph Boehmer, Hamdy M Embark, Anna Bauer, Monica Palmada, Chris H Yun, Edward J Weinman, Hitoshi Endou, Philip Cohen, Sven Lahme, Karl-Horst Bichler, Florian Lang
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 313 Issue 4 Pg. 998-1003 (Jan 23 2004) ISSN: 0006-291X [Print] United States
PMID14706641 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cytoskeletal Proteins
  • Dicarboxylic Acid Transporters
  • Immediate-Early Proteins
  • Nuclear Proteins
  • Organic Anion Transporters, Sodium-Dependent
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • SLC13A2 protein, human
  • Slc13a2 protein, rat
  • Slc9a3r2 protein, rat
  • Sodium-Hydrogen Exchangers
  • Symporters
  • sodium-hydrogen exchanger regulatory factor
  • Citric Acid
  • Succinic Acid
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • serum-glucocorticoid regulated kinase
Topics
  • Animals
  • Citric Acid (metabolism)
  • Cytoskeletal Proteins (genetics, metabolism)
  • Dicarboxylic Acid Transporters (genetics, metabolism)
  • Female
  • Humans
  • Immediate-Early Proteins
  • In Vitro Techniques
  • Kidney (metabolism)
  • Kidney Tubules, Proximal (metabolism)
  • Kinetics
  • Nuclear Proteins
  • Oocytes (drug effects, metabolism)
  • Organic Anion Transporters, Sodium-Dependent (genetics, metabolism)
  • Phosphoproteins (genetics, metabolism)
  • Protein Serine-Threonine Kinases (genetics, metabolism)
  • Proto-Oncogene Proteins (genetics, metabolism)
  • Proto-Oncogene Proteins c-akt
  • Rats
  • Recombinant Proteins (genetics, metabolism)
  • Sodium-Hydrogen Exchangers
  • Succinic Acid (pharmacology)
  • Symporters (genetics, metabolism)
  • Xenopus laevis

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