Regulation of ion channels by the serum- and glucocorticoid-inducible kinase SGK1

FASEB J. 2013 Jan;27(1):3-12. doi: 10.1096/fj.12-218230. Epub 2012 Sep 25.

Abstract

The ubiquitously expressed serum- and glucocorticoid-inducible kinase-1 (SGK1) is genomically regulated by cell stress (including cell shrinkage) and several hormones (including gluco- and mineralocorticoids). SGK1 is activated by insulin and growth factors through PI3K and 3-phosphoinositide-dependent kinase PDK1. SGK1 activates a wide variety of ion channels (e.g., ENaC, SCN5A, TRPV4-6, ROMK, Kv1.3, Kv1.5, Kv4.3, KCNE1/KCNQ1, KCNQ4, ASIC1, GluR6, ClCKa/barttin, ClC2, CFTR, and Orai/STIM), which participate in the regulation of transport, hormone release, neuroexcitability, inflammation, cell proliferation, and apoptosis. SGK1-sensitive ion channels participate in the regulation of renal Na(+) retention and K(+) elimination, blood pressure, gastric acid secretion, cardiac action potential, hemostasis, and neuroexcitability. A common (∼3-5% prevalence in Caucasians and ∼10% in Africans) SGK1 gene variant is associated with increased blood pressure and body weight as well as increased prevalence of type II diabetes and stroke. SGK1 further contributes to the pathophysiology of allergy, peptic ulcer, fibrosing disease, ischemia, tumor growth, and neurodegeneration. The effect of SGK1 on channel activity is modest, and the channels do not require SGK1 for basic function. SGK1-dependent ion channel regulation may thus become pathophysiologically relevant primarily after excessive (pathological) expression. Therefore, SGK1 may be considered an attractive therapeutic target despite its broad range of functions.

Publication types

  • Review

MeSH terms

  • Humans
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / physiology*
  • Ion Channel Gating
  • Ion Channels / physiology*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology*
  • Receptors, Glutamate / physiology

Substances

  • Immediate-Early Proteins
  • Ion Channels
  • Receptors, Glutamate
  • Protein-Serine-Threonine Kinases
  • serum-glucocorticoid regulated kinase