Activation of Na+/K+-ATPase by the serum and glucocorticoid-dependent kinase isoforms

Kidney Blood Press Res. 2002;25(6):370-4. doi: 10.1159/000068699.

Abstract

Background/aim: Expression of the constitutively active form of serum and glucocorticoid-dependent kinase ((S422D)SGK1) in Xenopus oocytes has recently been shown to upregulate endogenous Na(+)/K(+)-ATPase activity, an effect presumably participating in the regulation of cellular K(+) uptake and transepithelial Na(+) transport. SGK1 and the two isoforms SGK2 and SGK3 are stimulated by insulin and insulin-like growth factor-1 (IGF-1), which have been shown to enhance Na(+)/K(+)-ATPase activity in a variety of cells. The present experiments have been performed to elucidate whether or not wild-type SGK1, SGK2 and SGK3 are similar to (S422D)SGK1 in being effective regulators of Na(+)/K(+)-ATPase.

Methods: To this end, dual-electrode voltage clamp experiments were performed in Xenopus oocytes injected either with water or with mRNA of constitutively active (S422D)SGK1 and wild-type SGK1, SGK2 or SGK3. Na(+)/K(+)-ATPase activity was estimated from the outward-directed current created by readdition of extracellular K(+) in the presence of K(+) channel blocker Ba(2+) following a 10-min exposure to K(+)-free extracellular fluid.

Results: The outward-directed current was fully abolished by incubation with 1 mM ouabain and was significantly larger in oocytes expressing (S422D)SGK1, SGK1, SGK2 or SGK3, as compared to those injected with water.

Conclusion: The stimulating effect of SGK1 on the Xenopus oocyte Na(+)/K(+)-ATPase is mimicked by the isoforms SGK2 and SGK3. Thus, all three kinases may participate in the regulation of Na(+)/K(+)-ATPase activity by hormones such as insulin and IGF-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldosterone / metabolism
  • Animals
  • Barium / pharmacology
  • Biological Transport / drug effects
  • Biological Transport / physiology
  • Enzyme Inhibitors / pharmacology
  • Female
  • Glucocorticoids / metabolism
  • Humans
  • Immediate-Early Proteins
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Nuclear Proteins*
  • Oocytes / physiology
  • Ouabain / pharmacology
  • Patch-Clamp Techniques
  • Potassium Channel Blockers / pharmacology
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA, Complementary
  • Sodium / metabolism
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Xenopus laevis

Substances

  • Enzyme Inhibitors
  • Glucocorticoids
  • Immediate-Early Proteins
  • Isoenzymes
  • Nuclear Proteins
  • Potassium Channel Blockers
  • RNA, Complementary
  • Barium
  • Aldosterone
  • Ouabain
  • Sodium
  • Protein Serine-Threonine Kinases
  • serum-glucocorticoid regulated kinase
  • Sodium-Potassium-Exchanging ATPase