SGK

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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

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]

Related Research Articles

The transforming growth factor beta (TGFB) signaling pathway is involved in many cellular processes in both the adult organism and the developing embryo including cell growth, cell differentiation, apoptosis, cellular homeostasis and other cellular functions. In spite of the wide range of cellular processes that the TGFβ signaling pathway regulates, the process is relatively simple. TGFβ superfamily ligands bind to a type II receptor, which recruits and phosphorylates a type I receptor. The type I receptor then phosphorylates receptor-regulated SMADs (R-SMADs) which can now bind the coSMAD SMAD4. R-SMAD/coSMAD complexes accumulate in the nucleus where they act as transcription factors and participate in the regulation of target gene expression.

BMPR2

Bone morphogenetic protein receptor type II or BMPR2 is a serine/threonine receptor kinase. It binds Bone morphogenetic proteins, members of the TGF beta superfamily of ligands, which are involved in paracrine signalling. BMPs are involved in a host of cellular functions including osteogenesis, cell growth and cell differentiation. Signaling in the BMP pathway begins with the binding of a BMP to the type II receptor. This causes the recruitment of a BMP type I receptor, which it phosphorylates. The Type I receptor phosphorylates an R-SMAD a transcriptional regulator.

Endoglin

Endoglin (ENG) is a type I membrane glycoprotein located on cell surfaces and is part of the TGF beta receptor complex. It is also commonly referred to as CD105, END, FLJ41744, HHT1, ORW and ORW1. It has a crucial role in angiogenesis, therefore, making it an important protein for tumor growth, survival and metastasis of cancer cells to other locations in the body.

TGF beta receptor 1

Transforming growth factor beta receptor I is a membrane-bound receptor protein for the TGF beta superfamily of signaling ligands. TGFBR1 is its human gene.

TGF beta receptor 2

Transforming growth factor, beta receptor II (70/80kDa) is a TGF beta receptor. TGFBR2 is its human gene.

GSK3B

Glycogen synthase kinase 3 beta, also known as GSK3B, is an enzyme that in humans is encoded by the GSK3B gene. In mice, the enzyme is encoded by the GSK-3β gene. Abnormal regulation and expression of GSK3β is associated with an increased susceptibility towards bipolar disorder.

AKT2

AKT2, also known as RAC-beta serine/threonine-protein kinase, is an enzyme that in humans is encoded by the AKT2 gene. It influences metabolite storage as part of the insulin signal transduction pathway.

WNK1

WNK , also known as WNK1, is an enzyme that is encoded by the WNK1 gene. WNK1 is serine-threonine kinase and part of the "with no lysine/K" kinase WNK family. The predominant role of WNK1 is the regulation of cation-Cl− cotransporters (CCCs) such as the sodium chloride cotransporter (NCC), basolateral Na-K-Cl symporter (NKCC1), and potassium chloride cotransporter (KCC1) located within the kidney. CCCs mediate ion homeostasis and modulate blood pressure by transporting ions in and out of the cell. WNK1 mutations as a result have been implicated in blood pressure disorders/diseases; a prime example being familial hyperkalemic hypertension (FHHt).

SGK3

Serine/threonine-protein kinase Sgk3 is an enzyme that in humans is encoded by the SGK3 gene.

PRKD3

Serine/threonine-protein kinase D3 (PKD3) or PKC-nu is an enzyme that in humans is encoded by the PRKD3 gene.

STRAP

Serine-threonine kinase receptor-associated protein is an enzyme that in humans is encoded by the STRAP gene.

NEK6

Serine/threonine-protein kinase Nek6 is an enzyme that in humans is encoded by the NEK6 gene.

MAPK6

Mitogen-activated protein kinase 6 is an enzyme that in humans is encoded by the MAPK6 gene.

CAMKK1

Calcium/calmodulin-dependent protein kinase kinase 1 is an enzyme that in humans is encoded by the CAMKK1 gene.

CAMKK2

Calcium/calmodulin-dependent protein kinase kinase 2 is an enzyme that in humans is encoded by the CAMKK2 gene.

STK38L

Serine/threonine-protein kinase 38-like is an enzyme that in humans is encoded by the STK38L gene.

SGK2

Serine/threonine-protein kinase Sgk2 is an enzyme that in humans is encoded by the SGK2 gene.

INHBC

Inhibin beta C chain is a protein that in humans is encoded by the INHBC gene.

WNK3

Serine/threonine-protein kinase WNK3, also known as protein kinase lysine-deficient 3, is a protein that in humans is encoded by the WNK3 gene.

SGK1

Serine/threonine-protein kinase Sgk1 also known as serum and glucocorticoid-regulated kinase 1 is an enzyme that in humans is encoded by the SGK1 gene.

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. 1 2 "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.
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