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

Biochem Biophys Res Commun. 2004 Jan 23;313(4):998-1003. doi: 10.1016/j.bbrc.2003.12.011.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Citric Acid / metabolism
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Dicarboxylic Acid Transporters / genetics
  • Dicarboxylic Acid Transporters / metabolism*
  • Female
  • Humans
  • Immediate-Early Proteins
  • In Vitro Techniques
  • Kidney / metabolism*
  • Kidney Tubules, Proximal / metabolism
  • Kinetics
  • Nuclear Proteins*
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Organic Anion Transporters, Sodium-Dependent / genetics
  • Organic Anion Transporters, Sodium-Dependent / metabolism*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Rats
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sodium-Hydrogen Exchangers
  • Succinic Acid / pharmacology
  • Symporters / genetics
  • Symporters / metabolism*
  • Xenopus laevis


  • 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