SGK

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Serum/glucocorticoid regulated kinase 1
Rendering based on PDB 2R5T.
Available structures PDB 2R5T, 3HDM, 3HDN
Identifiers
Symbols	SGK1; SGK
External IDs	OMIM: 602958 MGI: 1340062 HomoloGene: 48364 GeneCards: SGK1 Gene
EC number	2.7.11.1
Gene Ontology Molecular function • nucleotide binding • protein serine/threonine kinase activity • calcium channel regulator activity • ATP binding • potassium channel regulator activity • sodium channel regulator activity • chloride channel regulator activity Cellular component • nucleus • cytoplasm • mitochondrion • endoplasmic reticulum • endoplasmic reticulum membrane • plasma membrane Biological process • regulation of cell growth • protein phosphorylation • sodium ion transport • response to stress • long-term memory • regulation of blood pressure • regulation of cell migration • positive regulation of transporter activity • regulation of cell proliferation • regulation of apoptotic process • regulation of catalytic activity • regulation of sequence-specific DNA binding transcription factor activity • regulation of gastric acid secretion • renal sodium ion absorption Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6446	20393
Ensembl	ENSG00000118515	ENSMUSG00000019970
UniProt	O00141	Q9WVC6
RefSeq (mRNA)	NM_001143676.1	NM_001161845.2
RefSeq (protein)	NP_001137148.1	NP_001155317.2
Location (UCSC)	Chr 6: 134.49 – 134.64 Mb	Chr 10: 21.6 – 21.72 Mb
PubMed search	[1]	[2]

Serine/threonine-protein kinase SGK is a kinase subfamily that is currently known as being encoded by SGK1, SGK2, and SGK3 genes.

Among the three SGK genes, SGK1 is the most intensively studied. This gene encodes a serine/threonine protein kinase that is highly similar to the rat serum-and glucocorticoid-induced protein kinase (SGK). This gene was identified in a screen of hepatocellular genes regulated in response to cellular hydration or swelling. Cellular hydration is a catabolic signal, stimulating glycogenolysis and proteolysis, and inhibiting protein and glycogen synthesis. This kinase has been shown to be important in activating certain potassium, sodium, and chloride channels. Expression of this gene in hepatocytes is stimulated by transforming growth factor-beta (TGF-beta) which participates in the pathophysiology of diabetic complications. Since both TGF-beta expression and SGK expression are elevated in diabetic nephropathy, this suggests an involvement of SGK in the development of this condition.

The SGK1 kinase regulates the myo-inositol transporter during osmotic stress.

Deregulated expression of SGK1 in the endometrium has been implicated in cases of infertility or recurrent miscarriage in humans, and SGK1 expression in the endometrium also affects fertility in mice.

Interactions

SGK has been shown to interact with Sodium-hydrogen exchange regulatory cofactor 2, Phosphoinositide-dependent kinase-1, Karyopherin alpha 2, MAPK7 and NEDD4.

A gain-of-function mutation in SGK1, or serum and glucocorticoid-inducible kinase 1, can lead to a shortening of the QT interval, which represents the repolarization time of the cardiac cells after a cardiac muscle contraction action potential. SGK1 does this by interacting with the KvLQT1 channel in cardiac cells, stimulating this channel when it is complex with KCNE1. SGK1 stimulates the slow delayed rectifier potassium current through this channel by phosphorylating PIKfyve, which consequently makes PI(3,5)P2 which goes on to increase the RAB11-dependent insertion of the KvLQT1/KCNE1 channels into the plasma membrane of cardiac neurons. SGK1 phosphorylates PIKfyve, which results in regulated channel activity through RAB11 dependent exocytosis of these KvLQT1/KCNE1 containing vesicles. Stress-induced stimuli have been known to activate SGK1, which demonstrates how Long QT Syndrome is brought on by stressors to the body or to the heart itself. By increasing the insertion of KVLQT1/KCNE1 channels into the plasma membrane through an alteration of trafficking within the cell, SGK1 is able to enhance the slow delayed potassium rectifier current in the neurons.

Further reading

• Lang F, Cohen P (2002). "Regulation and physiological roles of serum- and glucocorticoid-induced protein kinase isoforms". Sci. STKE 2001 (108): RE17. doi:10.1126/stke.2001.108.re17. PMID 11707620. 
• Kobayashi T, Cohen P (1999). "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". Biochem. J. 339 (2): 319–28. doi:10.1042/0264-6021:3390319. PMC 1220160. PMID 10191262. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1220160. 
• Park J, Leong ML, Buse P, et al. (1999). "Serum and glucocorticoid-inducible kinase (SGK) is a target of the PI 3-kinase-stimulated signaling pathway". EMBO J. 18 (11): 3024–33. doi:10.1093/emboj/18.11.3024. PMC 1171384. PMID 10357815. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1171384. 
• Kobayashi T, Deak M, Morrice N, Cohen P (2000). "Characterization of the structure and regulation of two novel isoforms of serum- and glucocorticoid-induced protein kinase". Biochem. J. 344 Pt 1 (Pt 1): 189–97. PMC 1220630. PMID 10548550. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1220630. 
• Guan KL, Figueroa C, Brtva TR, et al. (2000). "Negative regulation of the serine/threonine kinase B-Raf by Akt". J. Biol. Chem. 275 (35): 27354–9. doi:10.1074/jbc.M004371200. PMID 10869359. 
• Lang F, Klingel K, Wagner CA, et al. (2000). "Deranged transcriptional regulation of cell-volume-sensitive kinase hSGK in diabetic nephropathy". Proc. Natl. Acad. Sci. U.S.A. 97 (14): 8157–62. doi:10.1073/pnas.97.14.8157. PMC 16686. PMID 10884438. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=16686. 
• Brunet A, Park J, Tran H, et al. (2001). "Protein Kinase SGK Mediates Survival Signals by Phosphorylating the Forkhead Transcription Factor FKHRL1 (FOXO3a)". Mol. Cell. Biol. 21 (3): 952–65. doi:10.1128/MCB.21.3.952-965.2001. PMC 86685. PMID 11154281. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=86685. 
• Hayashi M, Tapping RI, Chao TH, et al. (2001). "BMK1 mediates growth factor-induced cell proliferation through direct cellular activation of serum and glucocorticoid-inducible kinase". J. Biol. Chem. 276 (12): 8631–4. doi:10.1074/jbc.C000838200. PMID 11254654. 
• Zhang BH, Tang ED, Zhu T, et al. (2001). "Serum- and glucocorticoid-inducible kinase SGK phosphorylates and negatively regulates B-Raf". J. Biol. Chem. 276 (34): 31620–6. doi:10.1074/jbc.M102808200. PMID 11410590. 
• Snyder PM, Olson DR, Thomas BC (2002). "Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated inhibition of the epithelial Na+ channel". J. Biol. Chem. 277 (1): 5–8. doi:10.1074/jbc.C100623200. PMID 11696533. 
• Debonneville C, Flores SY, Kamynina E, et al. (2002). "Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na+ channel cell surface expression". EMBO J. 20 (24): 7052–9. doi:10.1093/emboj/20.24.7052. PMC 125341. PMID 11742982. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=125341. 
• Yun CC, Chen Y, Lang F (2002). "Glucocorticoid activation of Na(+)/H(+) exchanger isoform 3 revisited. The roles of SGK1 and NHERF2". J. Biol. Chem. 277 (10): 7676–83. doi:10.1074/jbc.M107768200. PMID 11751930. 
• Lizcano JM, Deak M, Morrice N, et al. (2002). "Molecular basis for the substrate specificity of NIMA-related kinase-6 (NEK6). Evidence that NEK6 does not phosphorylate the hydrophobic motif of ribosomal S6 protein kinase and serum- and glucocorticoid-induced protein kinase in vivo". J. Biol. Chem. 277 (31): 27839–49. doi:10.1074/jbc.M202042200. PMID 12023960. 
• Waerntges S, Klingel K, Weigert C, et al. (2003). "Excessive transcription of the human serum and glucocorticoid dependent kinase hSGK1 in lung fibrosis". Cell. Physiol. Biochem. 12 (2–3): 135–42. doi:10.1159/000063790. PMID 12077559. 
• Busjahn A, Aydin A, Uhlmann R, et al. (2002). "Serum- and glucocorticoid-regulated kinase (SGK1) gene and blood pressure". Hypertension 40 (3): 256–60. doi:10.1161/01.HYP.0000030153.19366.26. PMID 12215463. 
• Brickley DR, Mikosz CA, Hagan CR, Conzen SD (2003). "Ubiquitin modification of serum and glucocorticoid-induced protein kinase-1 (SGK-1)". J. Biol. Chem. 277 (45): 43064–70. doi:10.1074/jbc.M207604200. PMID 12218062. 
• Itani OA, Liu KZ, Cornish KL, et al. (2002). "Glucocorticoids stimulate human sgk1 gene expression by activation of a GRE in its 5'-flanking region". Am. J. Physiol. Endocrinol. Metab. 283 (5): E971–9. doi:10.1152/ajpendo.00021.2002. PMID 12376324.