SGK

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Serum/glucocorticoid regulated kinase 1
Protein SGK1 PDB 2R5T.png
Rendering based on PDB 2R5T.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols SGK1 ; SGK
External IDs OMIM602958 MGI1340062 HomoloGene48364 ChEMBL: 2343 GeneCards: SGK1 Gene
EC number 2.7.11.1
RNA expression pattern
PBB GE SGK 201739 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 6446 20393
Ensembl ENSG00000118515 ENSMUSG00000019970
UniProt O00141 Q9WVC6
RefSeq (mRNA) NM_001143676 NM_001161845
RefSeq (protein) NP_001137148 NP_001155317
Location (UCSC) Chr 6:
134.49 – 134.64 Mb
Chr 10:
21.88 – 22 Mb
PubMed search [1] [2]

Serine/threonine-protein kinase SGK is a kinase subfamily that is known as being encoded by SGK1, SGK2, and SGK3 genes.[1][2]

Among the three SGK genes, the SGK1 gene 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, an involvement of SGK in the development of this condition is suggested.[3]

The SGK1 kinase regulates the myo-inositol transporter during osmotic stress.[4]

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.[5]

Interactions[edit]

SGK has been shown to interact with Sodium-hydrogen exchange regulatory cofactor 2,[6][7] Phosphoinositide-dependent kinase-1,[6][8] Karyopherin alpha 2,[9] MAPK7,[10] and NEDD4.[11][12]

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.[13] 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 then 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.[14] 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.[13]

References[edit]

  1. ^ Waldegger S, Barth P, Raber G, Lang F (May 1997). "Cloning and characterization of a putative human serine/threonine protein kinase transcriptionally modified during anisotonic and isotonic alterations of cell volume". Proc Natl Acad Sci U S A 94 (9): 4440–5. doi:10.1073/pnas.94.9.4440. PMC 20741. PMID 9114008. 
  2. ^ Waldegger S, Erdel M, Nagl UO, Barth P, Raber G, Steuer S, Utermann G, Paulmichl M, Lang F (November 1998). "Genomic organization and chromosomal localization of the human SGK protein kinase gene". Genomics 51 (2): 299–302. doi:10.1006/geno.1998.5258. PMID 9722955. 
  3. ^ "Entrez Gene: SGK serum/glucocorticoid regulated kinase". 
  4. ^ Klaus, F.; Palmada, M.; Lindner, R.; Laufer, J.; Jeyaraj, S.; Lang, F.; Boehmer, C. (2008). "Up-regulation of hypertonicity-activated myo-inositol transporter SMIT1 by the cell volume-sensitive protein kinase SGK1". The Journal of Physiology 586 (6): 1539–1547. doi:10.1113/jphysiol.2007.146191. PMC 2375683. PMID 18202099.  edit
  5. ^ Salker MS, Christian M, Steel JH, Nautiyal J, Lavery S, Trew G, Webster Z, Al-Sabbagh M, Puchchakayala G, Foller M, Landles C, Sharkey AM, Quenby S, Aplin JD, Regan L, Brosens JJ. (2011). "Deregulation of the serum- and glucocorticoid-inducible kinase SGK1 in the endometrium causes reproductive failure". Nat. Med. 16 (11): 1509–13. doi:10.1038/nm.2498. PMID 22001908. 
  6. ^ a b Chun, Jaesun; Kwon Taegun, Lee Eunjung, Suh Pann-Ghill, Choi Eui-Ju, Sun Kang Sang (October 2002). "The Na(+)/H(+) exchanger regulatory factor 2 mediates phosphorylation of serum- and glucocorticoid-induced protein kinase 1 by 3-phosphoinositide-dependent protein kinase 1". Biochem. Biophys. Res. Commun. (United States) 298 (2): 207–15. doi:10.1016/S0006-291X(02)02428-2. ISSN 0006-291X. PMID 12387817. 
  7. ^ Yun, C Chris; Chen Yueping, Lang Florian (March 2002). "Glucocorticoid activation of Na(+)/H(+) exchanger isoform 3 revisited. The roles of SGK1 and NHERF2". J. Biol. Chem. (United States) 277 (10): 7676–83. doi:10.1074/jbc.M107768200. ISSN 0021-9258. PMID 11751930. 
  8. ^ Park, J; Leong M L, Buse P, Maiyar A C, Firestone G L, Hemmings B A (June 1999). "Serum and glucocorticoid-inducible kinase (SGK) is a target of the PI 3-kinase-stimulated signaling pathway". EMBO J. (ENGLAND) 18 (11): 3024–33. doi:10.1093/emboj/18.11.3024. ISSN 0261-4189. PMC 1171384. PMID 10357815. 
  9. ^ Maiyar, Anita C; Leong Meredith L L, Firestone Gary L (March 2003). "Importin-α Mediates the Regulated Nuclear Targeting of Serum- and Glucocorticoid-inducible Protein Kinase (Sgk) by Recognition of a Nuclear Localization Signal in the Kinase Central Domain". Mol. Biol. Cell (United States) 14 (3): 1221–39. doi:10.1091/mbc.E02-03-0170. ISSN 1059-1524. PMC 151592. PMID 12631736. 
  10. ^ Hayashi, M; Tapping R I, Chao T H, Lo J F, King C C, Yang Y, Lee J D (March 2001). "BMK1 mediates growth factor-induced cell proliferation through direct cellular activation of serum and glucocorticoid-inducible kinase". J. Biol. Chem. (United States) 276 (12): 8631–4. doi:10.1074/jbc.C000838200. ISSN 0021-9258. PMID 11254654. 
  11. ^ Asher, Carol; Sinha Indranil, Garty Haim (May 2003). "Characterization of the interactions between Nedd4-2, ENaC, and sgk-1 using surface plasmon resonance". Biochim. Biophys. Acta (Netherlands) 1612 (1): 59–64. doi:10.1016/S0005-2736(03)00083-X. ISSN 0006-3002. PMID 12729930. 
  12. ^ Snyder, Peter M; Olson Diane R, Thomas Brittany C (January 2002). "Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated inhibition of the epithelial Na+ channel". J. Biol. Chem. (United States) 277 (1): 5–8. doi:10.1074/jbc.C100623200. ISSN 0021-9258. PMID 11696533. 
  13. ^ a b Seebohm, G.; Strutz-Seebohm, N.; Birkin, R.; Dell, G.; Bucci, C.; Spinosa, M. R.; Baltaev, R.; Mack, A. F.; Korniychuk, G.; Choudhury, A.; Marks, D.; Pagano, R. E.; Attali, B.; Pfeufer, A.; Kass, R. S.; Sanguinetti, M. C.; Tavare, J. M.; Lang, F. (2007). "Regulation of Endocytic Recycling of KCNQ1/KCNE1 Potassium Channels". Circulation Research 100 (5): 686–692. doi:10.1161/01.RES.0000260250.83824.8f. PMID 17293474.  edit
  14. ^ Seebohm, G.; Strutz-Seebohm, N.; Ureche, O. N.; Henrion, U.; Baltaev, R.; Mack, A. F.; Korniychuk, G.; Steinke, K.; Tapken, D.; Pfeufer, A.; Kääb, S.; Bucci, C.; Attali, B.; Merot, J.; Tavare, J. M.; Hoppe, U. C.; Sanguinetti, M. C.; Lang, F. (2008). "Long QT Syndrome-Associated Mutations in KCNQ1 and KCNE1 Subunits Disrupt Normal Endosomal Recycling of IKs Channels". Circulation Research 103 (12): 1451–1457. doi:10.1161/CIRCRESAHA.108.177360. PMID 19008479.  edit

Further reading[edit]