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


CONCLUSIONS
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.
Henke
Guido
G
Department of Physiology, University of Tübingen, Tübingen, Germany.
Setiawan
Iwan
I
Böhmer
Christoph
C
Lang
Florian
F
D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D009865:Oocytes / Q000502:physiology; D010042:Ouabain / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D018075:RNA, Complementary; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014982:Xenopus laevis; D000099184:Serum-Glucocorticoid Regulated Kinases
D000450:Aldosterone; D001464:Barium; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D017874:Immediate-Early Proteins; D007527:Isoenzymes; D009687:Nuclear Proteins; D010042:Ouabain; D026902:Potassium Channel Blockers; D017346:Protein Serine-Threonine Kinases; D018075:RNA, Complementary; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D000099184:Serum-Glucocorticoid Regulated Kinases