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Serine/threonine-protein kinases SGK represent a kinase subfamily with orthologs found across animal clades and in yeast[1] (compare Treefam family TF320906). In most vertebrates, including humans, there are three isoforms encoded by the genes SGK1, SGK2, and SGK3. The name Serum/glucocorticoid-regulated kinase refers to the first cloning of a SGK family member from a cDNA library screen for genes upregulated by the glucocorticoid dexamethasone in a rat mammary epithelial tumor cell line.[2] The first human family member (human SGK1) was cloned in a screen of hepatocellular genes regulated in response to cellular hydration or swelling.[3]

The term SGK is also used as a synonym for SGK1.[4]

Function

Main article: SGK1

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.[4]

The SGK1 kinase regulates the myo-inositol transporter during osmotic stress.[5]

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.[6]

References

  1. ^ Casamayor A, Torrance PD, Kobayashi T, Thorner J, Alessi DR (Feb 1999). "Functional counterparts of mammalian protein kinases PDK1 and SGK in budding yeast". Current Biology. 9 (4): 186–97. doi:10.1016/s0960-9822(99)80088-8. PMID 10074427.
  2. ^ Webster MK, Goya L, Ge Y, Maiyar AC, Firestone GL (Apr 1993). "Characterization of sgk, a novel member of the serine/threonine protein kinase gene family which is transcriptionally induced by glucocorticoids and serum". Molecular and Cellular Biology. 13 (4): 2031–40. doi:10.1128/mcb.13.4.2031. PMC 359524. PMID 8455596.
  3. ^ Waldegger S, Barth P, Raber G, Lang F (Apr 1997). "Cloning and characterization of a putative human serine/threonine protein kinase transcriptionally modified during anisotonic and isotonic alterations of cell volume". Proceedings of the National Academy of Sciences of the United States of America. 94 (9): 4440–5. Bibcode:1997PNAS...94.4440W. doi:10.1073/pnas.94.9.4440. PMC 20741. PMID 9114008.
  4. ^ a b "Entrez Gene: SGK serum/glucocorticoid regulated kinase".
  5. ^ Klaus F, Palmada M, Lindner R, Laufer J, Jeyaraj S, Lang F, Boehmer C (Mar 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.
  6. ^ Salker MS, Christian M, Steel JH, Nautiyal J, Lavery S, Trew G, Webster Z, Al-Sabbagh M, Puchchakayala G, Föller M, Landles C, Sharkey AM, Quenby S, Aplin JD, Regan L, Lang F, Brosens JJ (2011). "Deregulation of the serum- and glucocorticoid-inducible kinase SGK1 in the endometrium causes reproductive failure". Nature Medicine. 17 (11): 1509–13. doi:10.1038/nm.2498. hdl:10044/1/29492. PMID 22001908. S2CID 23062253.
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