Regulation and Physiological Roles of Serum- and Glucocorticoid-Induced Protein Kinase Isoforms

Sci. STKE, 13 November 2001
Vol. 2001, Issue 108, p. re17
DOI: 10.1126/stke.2001.108.re17

Regulation and Physiological Roles of Serum- and Glucocorticoid-Induced Protein Kinase Isoforms

  1. Florian Lang1 and
  2. Philip Cohen2
  1. 1Department of Physiology, University of Tubingen, Germany.
  2. 2Medical Research Council Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee, Scotland, DD1 4HN, United Kingdom.
  1. Contact authors: E-mail:p.cohen{at}dundee.ac.uk, florian.lang{at}uni-tuebingen.de

Abstract

Serum- and glucocorticoid-induced protein kinase 1 (SGK1) was identified in 1993 as an immediate early gene whose mRNA levels increase dramatically within 30 minutes when cells are exposed to serum or glucocorticoids, or both. Subsequently, many other agonists, acting through a variety of signal transduction pathways, have been shown to induce SGK1 gene transcription in cells and tissues. SGK1 is a member of the "AGC" subfamily, which includes protein kinases A, G, and C, and its catalytic domain is most similar to protein kinase B (PKB). Like PKB, SGK1 is activated by phosphorylation in response to signals that stimulate phosphatidylinositol 3-kinase, and this is mediated by 3-phosphoinositide-dependent protein kinase 1 (PDK1) and another protein kinase that has yet to be identified. Thus, SGK1 is remarkable in being activated at both the transcriptional and posttranslational levels by a huge number of extracellular signals. In contrast, little is known about the transcriptional regulation of the two closely related isoforms SGK2 and SGK3, although they can be activated by phosphorylation. The substrate specificity of SGK isoforms superficially resembles that of PKB in that serine and threonine residues lying in Arg-Xaa-Arg-Xaa-Xaa-Ser/Thr sequences (where Xaa is a variable amino acid) are phosphorylated. However, although they may have some substrates in common, evidence is emerging that SGK1 and PKB phosphorylate distinct proteins and have different functions in vivo. In particular, SGK1 plays an important role in activating certain potassium, sodium, and chloride channels, suggesting an involvement in the regulation of processes such as cell survival, neuronal excitability, and renal sodium excretion. Moreover, sustained high levels of SGK1 protein and activity may contribute to conditions such as hypertension and diabetic nephropathy. This raises the possibility that specific inhibitors of SGK1 may have therapeutic potential for the treatment of several diseases.

Citation:

F. Lang and P. Cohen, Regulation and Physiological Roles of Serum- and Glucocorticoid-Induced Protein Kinase Isoforms. Sci. STKE 2001, re17 (2001).

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