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Role of Serum and Glucocoritcoid [sic] inducible Kinase SGK1 in the regulation of glucose transport

von Dr. Sankarganesh Jeyaraj

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[1.] Sj/Fragment 017 01 - Diskussion
Zuletzt bearbeitet: 2016-11-25 11:31:25 Graf Isolan
Fragment, Gesichtet, Rajamanickam 2007, SMWFragment, Schutzlevel sysop, Sj, Verschleierung

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Hindemith
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Quelle: Rajamanickam 2007
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1.4 The Serum and Glucocorticoid inducible Kinase SGK1

The Serum and Glucocorticoid inducible protein Kinase 1 (SGK1) was originally cloned in 1993 as an immediate early gene transcriptionally stimulated by serum or glucocorticoids in rat and mammary tumor cells (81;82). Transcription of SGK1 was also shown to occur rapidly in response to many agonists like mineralocorticoids(83) , follicle stimulating hormone (FSH) (84), transforming growth factor (TGF- β) (85;86), thrombin (87), hypertonicity (88-90), high glucose (85;88) and neuronal injury or excitotoxicity (88;91;92)

SGK1 belongs to the ‘AGC’ subfamily of serine/threonine protein kinases, which include protein kinase A (PKA) or adenosine 3’, 5’ monophophate (cAMP)-dependent protein kinase, protein kinase G (PKG) or guanosine 3’, 5’ monophosphate (cGMP)-dependent protein kinase and isoforms of protein kinase C (PKC). SGK1 is present in the genomes of all eukaryotic organisms examined so far, including Caenorhabditis elegans, Drosphila, fish and mammals. Structure of SGK1 has been highly conserved through evolution like many other protein kinases (90;93;94).

Two other isoforms of SGK1 that have been identified in mammals and are named as SGK2 and SGK3. The catalytic domains of SGK2 and SGK3 isoforms share 80% amino acid sequence identity with one another and with SGK1 (89). The human gene encoding SGK1 was found in chromosome 6q23 (94) whereas the gene encoding SGK2 was identified in chromosome 20q12. SGK-like gene which encodes a protein having predicted amino acid sequence identical to that of human SGK3 (95) was found in chromosome 8q12.2.

SGK1 is expressed in humans that have been studied including the pancreas, liver, heart, lung, skeletal muscle, placenta, kidney and brain (90) but SGK1 is not expressed in all cell types within those tissues. For example, SGK1 transcript levels are found high in acinar cells in the pancreas (96). High transcript levels of SGK1 are also found in the distal tubule and collecting duct of the kidney and in thick ascending limb epithethial cells (85). The expression of SGK2 mRNA is restricted in human tissues. It expresses most abundantly in liver, kidney and pancreas (89). As like SGK1, SGK3 mRNA is present in all human and murine tissues examined but expression is particularly high in the mouse, heart and spleen and in the embryo (89;97).


81. Lang,F, Cohen,P: Regulation and physiological roles of serum- and glucocorticoid-induced protein kinase isoforms. Sci.STKE<. 2001:RE17, 2001

82. Webster,MK, Goya,L, Ge,Y, Maiyar,AC, Firestone,GL: Characterization of sgk, a novel member of the serine/threonine protein kinase gene family which is transcriptionally induced by glucocorticoids and serum. Mol.Cell Biol. 13:2031-2040, 1993

83. Brennan,FE, Fuller,PJ: Rapid upregulation of serum and glucocorticoid-regulated kinase (sgk) gene expression by corticosteroids in vivo. Mol.Cell Endocrinol. 166:129- 136, 2000

84. Alliston,TN, Maiyar,AC, Buse,P, Firestone,GL, Richards,JS: 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. Mol.Endocrinol. 11:1934-1949, 1997

85. Lang,F, Klingel,K, Wagner,CA, Stegen,C, Warntges,S, Friedrich,B, Lanzendorfer,M, Melzig,J, Moschen,I, Steuer,S, Waldegger,S, Sauter,M, Paulmichl,M, Gerke,V, Risler,T, Gamba,G, Capasso,G, Kandolf,R, Hebert,SC, Massry,SG, Broer,S: Deranged transcriptional regulation of cell-volume-sensitive kinase hSGK in diabetic nephropathy. Proc.Natl.Acad.Sci.U.S.A 97:8157-8162, 2000

86. Waldegger,S, Klingel,K, Barth,P, Sauter,M, Rfer,ML, Kandolf,R, Lang,F: h-sgk serinethreonine protein kinase gene as transcriptional target of transforming growth factor beta in human intestine. Gastroenterology 116:1081-1088, 1999

87. Kumar,S, Harvey,KF, Kinoshita,M, Copeland,NG, Noda,M, Jenkins,NA: cDNA cloning, expression analysis, and mapping of the mouse Nedd4 gene. Genomics 40:435-443, 1997

88. Bell,LM, Leong,ML, Kim,B, Wang,E, Park,J, Hemmings,BA, Firestone,GL: Hyperosmotic stress stimulates promoter activity and regulates cellular utilization of the serum- and glucocorticoid-inducible protein kinase (Sgk) by a p38 MAPKdependent pathway. J.Biol.Chem. 275:25262-25272, 2000

89. Kobayashi,T, Deak,M, Morrice,N, Cohen,P: Characterization of the structure and regulation of two novel isoforms of serum- and glucocorticoid-induced protein kinase. Biochem.J. 344 Pt 1:189-197, 1999

90. Waldegger,S, Barth,P, Raber,G, Lang,F: 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 94:4440-4445, 1997

91. Hollister,RD, Page,KJ, Hyman,BT: Distribution of the messenger RNA for the extracellularly regulated kinases 1, 2 and 3 in rat brain: effects of excitotoxic hippocampal lesions. Neuroscience 79:1111-1119, 1997

92. Imaizumi,K, Tsuda,M, Wanaka,A, Tohyama,M, Takagi,T: Differential expression of sgk mRNA, a member of the Ser/Thr protein kinase gene family, in rat brain after CNS injury. Brain Res.Mol.Brain Res. 26:189-196, 1994

93. Gonzalez-Robayna,IJ, Falender,AE, Ochsner,S, Firestone,GL, Richards,JS: Follicle- Stimulating hormone (FSH) stimulates phosphorylation and activation of protein kinase B (PKB/Akt) and serum and glucocorticoid-lnduced kinase (Sgk): evidence for A kinase-independent signaling by FSH in granulosa cells. Mol.Endocrinol. 14:1283- 1300, 2000

94. Waldegger,S, Erdel,M, Nagl,UO, Barth,P, Raber,G, Steuer,S, Utermann,G, Paulmichl,M, Lang,F: Genomic organization and chromosomal localization of the human SGK protein kinase gene. Genomics 51:299-302, 1998

95. Dai,F, Yu,L, He,H, Zhao,Y, Yang,J, Zhang,X, Zhao,S: Cloning and mapping of a novel human serum/glucocorticoid regulated kinase-like gene, SGKL, to chromosome 8q12.3-q13.1. Genomics 62:95-97, 1999

96. Klingel,K, Warntges,S, Bock,J, Wagner,CA, Sauter,M, Waldegger,S, Kandolf,R, Lang,F: Expression of cell volume-regulated kinase h-sgk in pancreatic tissue. Am.J.Physiol Gastrointest.Liver Physiol 279:G998-G1002, 2000

97. Liu,D, Yang,X, Songyang,Z: Identification of CISK, a new member of the SGK kinase family that promotes IL-3-dependent survival. Curr.Biol. 10:1233-1236, 2000

3.1 The Serum and Glucocorticoid inducible Kinase SGK1

The Serum and Glucocorticoid inducible protein Kinase 1 (SGK1) was identified in 1993 as an immediate early gene whose mRNA level increases noticeably within 30 minutes when mammary tumour or fibroblast cells are stimulated with serum or glucocorticoids1-3. SGK1 gene transcription was also shown to occur rapidly in response to many agonists like mineralocorticoids4-6, follicle stimulating hormone (FSH)7,8, transforming growth factor (TGF- β)9,10, thrombin11, hypertonicity12-14, high glucose9,11 and neuronal injury or excitotoxicity15,16.

SGK1 is a member of the ‘AGC’ subfamily of serine/threonine protein kinases, which include protein kinase A (PKA) or adenosine 3’, 5’ monophophate (cAMP)-dependent protein kinase, protein kinase G (PKG) or guanosine 3’, 5’ monophosphate (cGMP)-dependent protein kinase and isoforms of protein kinase C (PKC). SGK1 is present in the genomes of all eukaryotic organisms examined so far, including Caenorhabditis elegans, Drosphila, fish and mammals. Structure of SGK1 has been highly conserved through evolution like many other protein kinases8,13,17.

There are two other isoforms of SGK1 that have been identified in mammals and are named as SGK2 and SGK3. The catalytic domains of SGK2 and SGK3 isoforms share 80% amino acid sequence identity with one another and with SGK114. The human gene encoding SGK1 was found in chromosome 6q2317. The gene encoding SGK2 was identified in chromosome 20q12 and SGK-like gene which encodes a protein having predicted amino acid sequence identical to that of human SGK318 was found in chromosome 8q12.2.

SGK1 is expressed in all human tissues that have been studied including the pancreas, liver, heart, lung, skeletal muscle, placenta, kidney and brain13 but SGK1 is not expressed in all cell types within those tissues. For example, SGK1 transcript levels are found high in acinar cells in the pancreas19. High transcript levels of SGK1 are also found in the distal tubule and collecting duct of the kidney and in

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thick ascending limb epithethial cells9. The expression of SGK2 mRNA is restricted in human tissues. It express most abundantly in liver, kidney and pancreas20. As like SGK1, SGK3 mRNA is present in all human and murine tissues examined but expression is particularly high in the mouse heart and spleen and in the embryo20,21.


1. Lang,F. & Cohen,P. Regulation and physiological roles of serum- and glucocorticoid-induced protein kinase isoforms. Sci. STKE. 2001, RE17 (2001).

2. Webster,M.K., Goya,L. & Firestone,G.L. Immediate-early transcriptional regulation and rapid mRNA turnover of a putative serine/threonine protein kinase. J. Biol. Chem. 268, 11482-11485 (1993).

3. Webster,M.K., Goya,L., Ge,Y., Maiyar,A.C. & Firestone,G.L. Characterization of sgk, a novel member of the serine/threonine protein kinase gene family which is transcriptionally induced by glucocorticoids and serum. Mol. Cell Biol. 13, 2031-2040 (1993).

4. Brennan,F.E. & Fuller,P.J. Rapid upregulation of serum and glucocorticoidregulated kinase (sgk) gene expression by corticosteroids in vivo. Mol. Cell Endocrinol. 166, 129-136 (2000).

5. Chen,S.Y. et al. Epithelial sodium channel regulated by aldosterone-induced protein sgk. Proc. Natl. Acad. Sci. U. S. A 96, 2514-2519 (1999).

6. Shigaev,A., Asher,C., Latter,H., Garty,H. & Reuveny,E. Regulation of sgk by aldosterone and its effects on the epithelial Na(+) channel. Am. J. Physiol Renal Physiol 278, F613-F619 (2000).

7. Alliston,T.N., Maiyar,A.C., Buse,P., Firestone,G.L. & Richards,J.S. 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. Mol. Endocrinol. 11, 1934-1949 (1997).

8. Gonzalez-Robayna,I.J., Falender,A.E., Ochsner,S., Firestone,G.L. & Richards,J.S. Follicle-Stimulating hormone (FSH) stimulates phosphorylation and activation of protein kinase B (PKB/Akt) and serum and glucocorticoid-lnduced kinase (Sgk): evidence for A kinase-independent signaling by FSH in granulosa cells. Mol. Endocrinol. 14, 1283-1300 (2000).

9. Lang,F. et al. Deranged transcriptional regulation of cell-volume-sensitive kinase hSGK in diabetic nephropathy. Proc. Natl. Acad. Sci. U. S. A 97, 8157- 8162 (2000).

10. Waldegger,S. et al. h-sgk serine-threonine protein kinase gene as transcriptional target of transforming growth factor beta in human intestine. Gastroenterology 116, 1081-1088 (1999).

11. Kumar,J.M., Brooks,D.P., Olson,B.A. & Laping,N.J. Sgk, a putative serine/threonine kinase, is differentially expressed in the kidney of diabetic mice and humans. J. Am. Soc. Nephrol. 10, 2488-2494 (1999).

12. Bell,L.M. et al. Hyperosmotic stress stimulates promoter activity and regulates cellular utilization of the serum- and glucocorticoid-inducible protein kinase (Sgk) by a p38 MAPK-dependent pathway. J. Biol. Chem. 275, 25262-25272 (2000).

13. Waldegger,S., Barth,P., Raber,G. & Lang,F. 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, 4440-4445 (1997).

14. Kobayashi,T., Deak,M., Morrice,N. & Cohen,P. Characterization of the structure and regulation of two novel isoforms of serum- and glucocorticoidinduced protein kinase. Biochem. J. 344 Pt 1, 189-197 (1999).

15. Hollister,R.D., Page,K.J. & Hyman,B.T. Distribution of the messenger RNA for the extracellularly regulated kinases 1, 2 and 3 in rat brain: effects of excitotoxic hippocampal lesions. Neuroscience 79, 1111-1119 (1997).

16. Imaizumi,K., Tsuda,M., Wanaka,A., Tohyama,M. & Takagi,T. Differential expression of sgk mRNA, a member of the Ser/Thr protein kinase gene family, in rat brain after CNS injury. Brain Res. Mol. Brain Res. 26, 189-196 (1994).

17. Waldegger,S. et al. Genomic organization and chromosomal localization of the human SGK protein kinase gene. Genomics 51, 299-302 (1998).

18. Dai,F. et al. Cloning and mapping of a novel human serum/glucocorticoid regulated kinase-like gene, SGKL, to chromosome 8q12.3-q13.1. Genomics 62, 95-97 (1999).

19. Klingel,K. et al. Expression of cell volume-regulated kinase h-sgk in pancreatic tissue. Am. J. Physiol Gastrointest. Liver Physiol 279, G998-G1002 (2000).

20. Kobayashi,T. & Cohen,P. 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 ( Pt 2), 319-328 (1999).

21. Liu,D., Yang,X. & Songyang,Z. Identification of CISK, a new member of the SGK kinase family that promotes IL-3-dependent survival. Curr. Biol. 10, 1233-1236 (2000).

Anmerkungen

The source is not given.

Sichter
(Hindemith) LieschenMueller



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