The serine/threonine kinases SGK2 and SGK3 are potent stimulators of the epithelial Na+ channel α,β,γ-ENaC

  title={The serine/threonine kinases SGK2 and SGK3 are potent stimulators of the epithelial Na+ channel $\alpha$,$\beta$,$\gamma$-ENaC},
  author={Bj{\"o}rn Friedrich and Y. Feng and Philip Cohen and Teut Risler and Alain Vandewalle and Stefan Br{\"o}er and J Wang and David Pearce and Florian Lang},
  journal={Pfl{\"u}gers Archiv},
The serum- and glucocorticoid-inducible kinase 1 (SGK1) has been identified as a signalling molecule up-regulated by aldosterone, which stimulates the renal epithelial Na+ channel ENaC. It is therefore thought to participate in the antinatriuretic action of this hormone. More recently, two isoforms, SGK2 and SGK3, have been cloned. The present study was performed to establish whether SGK2 and SGK3 influence ENaC activity similarly to SGK1. Dual-electrode voltage-clamp experiments in Xenopus… 
Protein Kinase B Alpha (PKBα) Stimulates the Epithelial Sodium Channel (ENaC) Heterologously Expressed in Xenopus laevis Oocytes by Two Distinct Mechanisms
It is concluded that the acute stimulatory effect of P KBΑ involves a specific kinase consensus motif in the C-terminus of the channel’s Α-subunit, and the increase in channel surface expression caused by co-expression of PKBΑ is probably mediated by an effect on channel trafficking.
NH2 terminus of serum and glucocorticoid-regulated kinase 1 binds to phosphoinositides and is essential for isoform-specific physiological functions.
Observations support the idea that the NH(2)-terminal domain acts downstream of PI 3-kinase-dependent activation to target the kinase to specific cellular compartments and/or substrates, possibly through its interactions with a subset of phosphoinositides.
Protein Kinase SGK2 Is Induced by the β3 Adrenergic Receptor-cAMP-PKA-PGC-1α/NT-PGC-1α Axis but Dispensable for Brown/Beige Adipose Tissue Thermogenesis
Results reveal a new signaling component SGK2, although dispensable for cold-induced thermogenesis that adds an additional layer of complexity to the β3AR signaling network in brown/beige adipose tissue.
(Patho)physiological significance of the serum- and glucocorticoid-inducible kinase isoforms.
The serum- and glucocorticoid-inducible kinase-1 (SGK1) is ubiquitously expressed and under genomic control by cell stress and hormones, and may play an active role in a multitude of pathophysiological conditions.
Association of the Serum and Glucocorticoid Regulated Kinase (sgk1) Gene with QT Interval
The regulation of KCNE1/KCNQ1 by SGK1 is similarly relevant for the repolarization of cardiac myocytes as for regulation of renal ENaC activity and blood pressure control.
Down-Regulation of the Epithelial Na+ Channel ENaC by Janus kinase 2
JAK2 is a powerful inhibitor of ENaC, which was determined from amiloride (50 μM)-sensitive current (Iamil) in dual electrode voltage clamp and was significantly enhanced in colonic epithelium and Ussing chambers.
Additive regulation of GluR1 by stargazin and serum- and glucocorticoid-inducible kinase isoform SGK3
SGK3 and stargazin regulate GluR1 independently, and thus, their effects on glutamate-induced currents are additive.
Renal function of gene-targeted mice lacking both SGK1 and SGK3.
  • F. Grahammer, F. Artunc, F. Lang
  • Biology, Medicine
    American journal of physiology. Regulatory, integrative and comparative physiology
  • 2006
Serum- and glucocorticoid-inducible kinase (SGK) 1 and SGK3 share the ability to upregulate several ion channels, including the epithelial Na(+) channel, and the possibility was considered that SGK1 andSGK3 could mutually replace each other, thus preventing severe NaCl loss in sgk1(+/+)/sgk3(-/-) mice.
Regulation of the glutamate transporter EAAT1 by the ubiquitin ligase Nedd4‐2 and the serum and glucocorticoid‐inducible kinase isoforms SGK1/3 and protein kinase B
A powerful novel mechanism that regulates the activity of EAAT1 is revealed, which might participate in the regulation of neuronal excitability and glutamate transport in other tissues.


The Serum and Glucocorticoid Kinase sgk Increases the Abundance of Epithelial Sodium Channels in the Plasma Membrane of Xenopus Oocytes*
The experiments indicate that sgk stimulates electrogenic sodium transport by increasing the number of ENaCs at the cell surface and suggest that s gk may mediate the early increase in aldosterone-induced sodium current.
Regulation of sgk by aldosterone and its effects on the epithelial Na(+) channel.
regulation of sgk by aldosterone in native mammalian epithelia and its effect on ENaC are characterized to suggest that the response is mediated, at least in part, by occupancy of the mineralocorticoid receptor.
Serum and glucocorticoid‐inducible kinase (SGK) is a target of the PI 3‐kinase‐stimulated signaling pathway
Evidence is presented that SGK is a component of the phosphoinositide 3 (PI 3)‐kinase signaling pathway and that hyperphosphorylation of endogenous SGK, and promoted translocation to the nucleus could be inhibited by wortmannin, but not by rapamycin.
Characterization of the structure and regulation of two novel isoforms of serum- and glucocorticoid-induced protein kinase.
Two novel isoforms of SGK are identified, termed SGK2 and SGK3, whose catalytic domains share 80% amino acid sequence identity with each other and with SGK (renamed SGK1), and are activated in vitro by PDK1 and in vivo in response to signals that activate phosphatidylinositol (PI) 3-kinase.
sgk Is an Aldosterone-induced Kinase in the Renal Collecting Duct
It is reported here that aldosterone rapidly increases mRNA levels of a putative Ser/Thr kinase,sgk (or serum- andglucocorticoid-regulated kinase), in its native target cells, i.e. in cortical collecting duct cells, and this protein kinase plays an important role in the early phase of ald testosterone-stimulated Na+ transport.
Epithelial sodium channel regulated by aldosterone-induced protein sgk.
Sgk (serum and glucocorticoid-regulated kinase), a member of the serine-threonine kinase family, is identified as an aldosterone-induced regulator of ENaC activity, suggesting that sgk plays a central role in ald testosterone regulation of Na+ absorption and thus in the control of extracellular fluid volume, blood pressure, and sodium homeostasis.
h-sgk Serine-Threonine Protein Kinase as Transcriptional Target of p38/MAP Kinase pathway in HepG2 Human Hepatoma Cells
The stimulation of h-sgk transcription by osmotic cell shrinkage is mediated by p38-kinase, which constitutes a part of the osmosensor in the yeast Saccharomyces cerevisiae.
Characterization of sgk, a novel member of the serine/threonine protein kinase gene family which is transcriptionally induced by glucocorticoids and serum.
This is the first report of a presumed serine/threonine protein kinase that is highly regulated at the transcriptional level by glucocorticoid hormones and suggests a novel interplay between glucoc Corticoid receptor signalling and aprotein kinase of the second messenger family.
Cloning of sgk serine-threonine protein kinase from shark rectal gland – a gene induced by hypertonicity and secretagogues
The shark sgk-1 serine-threonine protein kinase may provide a link between cell volume, Cl–secretion and protein phosphorylation state in shark rectal gland cells.
Activation of serum- and glucocorticoid-regulated protein kinase by agonists that activate phosphatidylinositide 3-kinase is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) and PDK2.
It is shown that PDK1 activates SGK in vitro by phosphorylating Thr256, and the findings raise the possibility that some physiological roles ascribed to PKB on the basis of the overexpression of constitutively active PKB mutants might be mediated by SGK.