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

  title={Regulation and Physiological Roles of Serum- and Glucocorticoid-Induced Protein Kinase Isoforms},
  author={Florian Lang and Philip Cohen},
  journal={Science's STKE},
  pages={re17 - re17}
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… 
Stimulus-Dependent Regulation of Serum and Glucocorticoid Inducible Protein Kinase (SGK) Transcription, Subcellular Localization and Enzymatic Activity
We originally discovered the serum and glucocorticoid inducible protein kinase, SGK, as a novel protein kinase that is under acute transcriptional control by serum and glucocorticoids. An expanding
Ubiquitin Modification of Serum and Glucocorticoid-induced Protein Kinase-1 (SGK-1)*
It is demonstrated for the first time that the low steady-state expression level of SGK-1 is due to polyubiquitination and subsequent degradation by the 26S proteasome, which is consistent with the recently described role of SGk-1 in phosphorylating the membrane-associated protein Nedd4-2 and the integral membrane Na+/H+ exchanger isoform 3 (NHE3).
(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.
Serum and glucocorticoid inducible kinase, metabolic syndrome, inflammation, and tumor growth
SGK1 sensitive functions contribute to regulation of epithelial transport, excitability, degranulation, matrix protein deposition, coagulation, platelet aggregation, migration, cell proliferation, and apoptosis, and apparently, SGK1 is not required for housekeeping functions.
Serum and Glucocorticoid-Regulated Kinase Signaling in Breast Cancer
The studies show that the serum and glucocorticoid-regulated kinases (SGKs) can function as effectors of PI 3-kinase and transduce signals to phenotypes associated with malignancy and identify the mechanism by which SGK3 is activated downstream of PIK3CA, specifically through the catalytic activity of the phosphoinositide phosphatase INPP4B.
Ubiquitin-proteasome degradation of serum- and glucocorticoid-regulated kinase-1 (SGK-1) is mediated by the chaperone-dependent E3 ligase CHIP.
It is reported that SGK-1 forms a complex with the stress-associated E3 ligase CHIP [C-terminus of Hsc (heat-shock cognate protein) 70-interacting protein]; CHIP is required for both the ubiquitin modification and rapid proteasomal degradation of SGK -1.
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.
Differential Regulation of Serum- and Glucocorticoid-Inducible Kinase 1 (SGK1) Splice Variants Based on Alternative Initiation of Transcription
The present observations disclose the transcription of three distinct SGK1 splice variants, which are all markedly upregulated in tumor tissue but differentially upregulated following differentiation or hypoxia.
Serum- and glucocorticoid-inducible kinase 1 (SGK1) mediates glucocorticoid-induced inhibition of insulin secretion.
It is shown that dexamethasone upregulates transcription and expression of the serum- and glucocorticoid-inducible kinase 1 (SGK1) in insulin-secreting cells, an effect reversed by mifepristone (RU486), an antagonist of the nuclear glucoc Corticoid receptor.
PDK1, the master regulator of AGC kinase signal transduction.


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.
Activation of Serum- and Glucocorticoid-induced Protein Kinase (Sgk) by Cyclic AMP and Insulin*
It is demonstrated that incubation of transfected cells with 8-(4-chlorophenylthio)-cAMP led to a 2-fold activation of recombinant Sgk expressed in COS7 cells, and the combination of insulin plus 8CPT-cAMP elicited a larger response than either agent alone.
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 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.
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.
Follicle stimulating hormone-regulated expression of serum/glucocorticoid-inducible kinase in rat ovarian granulosa cells: a functional role for the Sp1 family in promoter activity.
The novel, biphasic induction of sgk that correlates with granulosa cell progression from proliferation to differentiation appears to involve sequential, coordinated actions of FSH, PKA, and transcription factors, including Sp1 and Sp3.
Expression and localization of serum/glucocorticoid-induced kinase in the rat ovary: relation to follicular growth and differentiation.
Results show that FSH and LH stimulate marked increases in the cellular content of Sgk, as well as dramatic changes in the subcellular distribution of this kinase.
Hyperosmotic Stress Stimulates Promoter Activity and Regulates Cellular Utilization of the Serum- and Glucocorticoid-inducible Protein Kinase (Sgk) by a p38 MAPK-dependent Pathway*
It is proposed that the stimulated expression of enzymatically active Sgk after sorbitol treatment is a newly defined component of the p38 MAPK-mediated response to hyperosmotic stress.