Regulation of KCNE1-dependent K+ current by the serum and glucocorticoid-inducible kinase (SGK) isoforms

  title={Regulation of KCNE1-dependent K+ current by the serum and glucocorticoid-inducible kinase (SGK) isoforms},
  author={Hamdy M. Embark and Christoph B{\"o}hmer and Volker Vallon and Friedrich C. Luft and Florian Lang},
  journal={Pfl{\"u}gers Archiv},
The slowly activating K+ channel subunit KCNE1 is expressed in a variety of tissues including proximal renal tubules, cardiac myocytes and stria vascularis of inner ear. The present study has been performed to explore whether the serum- and glucocorticoid-inducible kinase family members SGK1, SGK2, or SGK3 and/or protein kinase B (PKB) influence K+ channel activity in Xenopus oocytes expressing KCNE1. cRNA encoding KCNE1 was injected with or without cRNA encoding wild-type SGK1, constitutively… 

Serum- and Glucocorticoid-inducible Kinases (SGK) regulate KCNQ1/KCNE potassium channels

Investigation to KCNQ1/KCNE3 channels and their modulation by SGKs shows that these channels are not stimulated by any of the three SGK isoforms when expressed in a heterologous expression system, suggesting a key region important for channel complex sorting into vesicles.

New insights into the role of serum- and glucocorticoid-inducible kinase SGK1 in the regulation of renal function and blood pressure

  • V. VallonF. Lang
  • Biology, Medicine
    Current opinion in nephrology and hypertension
  • 2005
PPARγ activators may increase renal Na+ reabsorption by stimulating SGK1 and ENaC andSGK1 may affect renal transport mechanisms beyond Na+Reabsorption and K+ secretion in ASDN and may be relevant to the pathophysiology of hypertension and other diseases.

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.

Upregulation of HERG Channels by the Serum and Glucocorticoid Inducible Kinase Isoform SGK3

SGK3 participates in the regulation of HERG by increasing HERG protein abundance in the plasma membrane and may thus modify the duration of the cardiac action potential.

Deranged Kv channel regulation in fibroblasts from mice lacking the serum and glucocorticoid inducible kinase SGK1

In conclusion, lack of SGK1 does not abrogate Kv channel activity but abolishes regulation of those channels by serum, glucocorticoid and IGF‐1, an effect influencing capacitative Ca2+ entry in sgk1+/+ MTF, whereas in s gk1−/− cells it remained unchanged.

Serum- and glucocorticoid-inducible kinase 1 in the regulation of renal and extrarenal potassium transport

SGK1-dependent regulation of K+ channels and K+ transport contributes to the stimulation of renal K+ excretion following high K+ intake, to insulin-induced cellular K+ uptake and hypokalemia, to inhibition of insulin release by glucocorticoids, to stimulation of mast cell degranulation and gastric acid secretion, and to cardiac repolarization.

Long QT Syndrome – Associated Mutations in KCNQ 1 and KCNE 1 Subunits Disrupt Normal Endosomal Recycling of I Ks Channels

Identification of the IKs recycling pathway and its modulation by stress-stimulated SGK1 provides novel mechanistic insight into potentially fatal cardiac arrhythmias triggered by physical or psychological stress.

Regulation of Channels by the Serum and Glucocorticoid-Inducible Kinase - Implications for Transport, Excitability and Cell Proliferation

The serum and glucocorticoid-inducible kinase SGK1 stimulates the Na+ channels ENaC and SCN5A, the K+ channels ROMK1, Kv1.3, and KCNE1/KCNQ1, the cation conductance induced by 4F2/LAT1 and the

AMP-activated protein kinase inhibits KCNQ1 channels through regulation of the ubiquitin ligase Nedd4-2 in renal epithelial cells.

Results indicate that AMPK inhibits KCNQ1 activity by promoting Nedd4-2-dependent channel ubiquitination and retrieval from the plasma membrane.



K+ channel activation by all three isoforms of serum- and glucocorticoid-dependent protein kinase SGK

A powerful stimulating effect of all three isoforms of SGK on K+ channels is revealed, which may participate in regulation of epithelial transport, cell proliferation, and neuromuscular excitability.

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.

IGF-1 up-regulates K+ channels via PI3-kinase, PDK1 and SGK1

In conclusion, IGF-1 through PI3-kinase, PDK1 and SGK1 up-regulates Kv channels, an effect required for the proliferative action of the growth factor.

Effects of the Serine/Threonine Kinase SGK1 on the Epithelial Na+ Channel (ENaC) and CFTR: Implications for Cystic Fibrosis

Enhanced expression of h-SGK1 in epithelial cells of CF-lung tissue may be a novel pathophysiological factor contributing to increased Na+ channel activity and thus to increasedNa+ transport in CF.

Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel.

K(V)LQT1 is the subunit that coassembles with minK to form I(Ks) channels and I( Ks) dysfunction is a cause of cardiac arrhythmia.

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.

Inhibition of cardiac delayed rectifier K+ currents by an antisense oligodeoxynucleotide against IsK (minK) and over-expression of IsK mutant D77N in neonatal mouse hearts

Results indicate that the IsK protein associates with both KvLQT1 and ERG products to modulate IKr and IKs in cardiac myocytes.

KCNE1 reverses the response of the human K+ channel KCNQ1 to cytosolic pH changes and alters its pharmacology and sensitivity to temperature

These results show that coexpression of KCNE1 reversed pH regulation of KCNQ1 from inhibition to activation by acidic pHi, and altered the pharmacological properties and sensitivity to temperature of KCnQ1.

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.

Coassembly of KVLQT1 and minK (IsK) proteins to form cardiac IKS potassium channel

KVLQT1 is the subunit that coassembles with minK to form IKS channels and IKS dysfunction is a cause of cardiac arrhythmia, and is shown to encode a K+ channel with biophysical properties unlike other known cardiac currents.