|
|
||||||||
Department of Physiology, University of Tuebingen, Tuebingen, Germany; and Departments of Medicine and Pharmacology, University of California San Diego and San Diego Veterans Affairs Healthcare System, San Diego, California
The serum- and glucocorticoid-inducible kinase-1 (SGK1) is ubiquitously expressed and under genomic control by cell stress (including cell shrinkage) and hormones (including gluco- and mineralocorticoids). Similar to its isoforms SGK2 and SGK3, SGK1 is activated by insulin and growth factors via phosphatidylinositol 3-kinase and the 3-phosphoinositide-dependent kinase PDK1. SGKs activate ion channels (e.g., ENaC, TRPV5, ROMK, Kv1.3, KCNE1/KCNQ1, GluR1, GluR6), carriers (e.g., NHE3, GLUT1, SGLT1, EAAT15), and the Na+-K+-ATPase. They regulate the activity of enzymes (e.g., glycogen synthase kinase-3, ubiquitin ligase Nedd42, phosphomannose mutase-2) and transcription factors (e.g., forkhead transcription factor FKHRL1,
-catenin, nuclear factor
B). SGKs participate in the regulation of transport, hormone release, neuroexcitability, cell proliferation, and apoptosis. SGK1 contributes to Na+ retention and K+ elimination of the kidney, mineralocorticoid stimulation of salt appetite, glucocorticoid stimulation of intestinal Na+/H+ exchanger and nutrient transport, insulin-dependent salt sensitivity of blood pressure and salt sensitivity of peripheral glucose uptake, memory consolidation, and cardiac repolarization. A common (
5% prevalence) SGK1 gene variant is associated with increased blood pressure and body weight. SGK1 may thus contribute to metabolic syndrome. SGK1 may further participate in tumor growth, neurodegeneration, fibrosing disease, and the sequelae of ischemia. SGK3 is required for adequate hair growth and maintenance of intestinal nutrient transport and influences locomotive behavior. In conclusion, the SGKs cover a wide variety of physiological functions and may play an active role in a multitude of pathophysiological conditions. There is little doubt that further targets will be identified that are modulated by the SGK isoforms and that further SGK-dependent in vivo physiological functions and pathophysiological conditions will be defined.
This article has been cited by other articles:
![]() |
H. Staiger, F. Machicao, A. Fritsche, and H.-U. Haring Pathomechanisms of Type 2 Diabetes Genes Endocr. Rev., October 1, 2009; 30(6): 557 - 585. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Sobiesiak, E. Shumilina, R. S. Lam, F. Wolbing, N. Matzner, S. Kaesler, I. M. Zemtsova, A. Lupescu, N. Zahir, D. Kuhl, et al. Impaired Mast Cell Activation in Gene-Targeted Mice Lacking the Serum- and Glucocorticoid-Inducible Kinase SGK1 J. Immunol., October 1, 2009; 183(7): 4395 - 4402. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Bhandaru, D. S. Kempe, A. Rotte, R. Rexhepaj, D. Kuhl, and F. Lang Hyperaldosteronism, hypervolemia, and increased blood pressure in mice expressing defective APC Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2009; 297(3): R571 - R575. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Vallon, J. Schroth, F. Lang, D. Kuhl, and S. Uchida Expression and phosphorylation of the Na+-Cl- cotransporter NCC in vivo is regulated by dietary salt, potassium, and SGK1 Am J Physiol Renal Physiol, September 1, 2009; 297(3): F704 - F712. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. G. Proud Dynamic Balancing: DEPTOR Tips the Scales J Mol Cell Biol, August 25, 2009; (2009) mjp012v1. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Melhem, S. D. Yamada, G. F. Fleming, B. Delgado, D. R. Brickley, W. Wu, M. Kocherginsky, and S. D. Conzen Administration of Glucocorticoids to Ovarian Cancer Patients Is Associated with Expression of the Anti-apoptotic Genes SGK1 and MKP1/DUSP1 in Ovarian Tissues Clin. Cancer Res., May 1, 2009; 15(9): 3196 - 3204. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. R. Alessi, L. R. Pearce, and J. M. Garcia-Martinez New Insights into mTOR Signaling: mTORC2 and Beyond Sci. Signal., April 21, 2009; 2(67): pe27 - pe27. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. F. Ackermann, K. M. Boini, H. Volkl, M. Bhandaru, P. M. Bareiss, L. Just, V. Vallon, K. Amann, D. Kuhl, Y. Feng, et al. SGK1-sensitive renal tubular glucose reabsorption in diabetes Am J Physiol Renal Physiol, April 1, 2009; 296(4): F859 - F866. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. H. Kim, K. X. Kim, N. N. Raveendran, T. Wu, S. R. Pondugula, and D. C. Marcus Regulation of ENaC-mediated sodium transport by glucocorticoids in Reissner's membrane epithelium Am J Physiol Cell Physiol, March 1, 2009; 296(3): C544 - C557. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. A. Soukas, E. A. Kane, C. E. Carr, J. A. Melo, and G. Ruvkun Rictor/TORC2 regulates fat metabolism, feeding, growth, and life span in Caenorhabditis elegans Genes & Dev., February 15, 2009; 23(4): 496 - 511. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. J. C. Tai, C.-C. Su, Y.-L. Ma, and E. H. Y. Lee SGK1 Phosphorylation of I{kappa}B Kinase {alpha} and p300 Up-regulates NF-{kappa}B Activity and Increases N-Methyl-D-aspartate Receptor NR2A and NR2B Expression J. Biol. Chem., February 13, 2009; 284(7): 4073 - 4089. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. J. Mullins, A. Peter, N. Wrobel, J. R. McNeilly, A. S. McNeilly, E. A. S. Al-Dujaili, D. G. Brownstein, J. J. Mullins, and C. J. Kenyon Cyp11b1 Null Mouse, a Model of Congenital Adrenal Hyperplasia J. Biol. Chem., February 6, 2009; 284(6): 3925 - 3934. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Chen, Y. Chen, B.-e Xu, Y.-C. Juang, S. Stippec, Y. Zhao, and M. H. Cobb Regulation of a Third Conserved Phosphorylation Site in SGK1 J. Biol. Chem., February 6, 2009; 284(6): 3453 - 3460. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. E Hills, P. E Squires, and R. Bland Serum and glucocorticoid regulated kinase and disturbed renal sodium transport in diabetes J. Endocrinol., December 1, 2008; 199(3): 343 - 349. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Artunc, O. Nasir, K. Amann, K. M. Boini, H.-U. Haring, T. Risler, and F. Lang Serum- and glucocorticoid-inducible kinase 1 in doxorubicin-induced nephrotic syndrome Am J Physiol Renal Physiol, December 1, 2008; 295(6): F1624 - F1634. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. S. Raikwar, P. M. Snyder, and C. P. Thomas An evolutionarily conserved N-terminal Sgk1 variant with enhanced stability and improved function Am J Physiol Renal Physiol, November 1, 2008; 295(5): F1440 - F1448. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Sheng, T. Sun, B. Cong, P. He, Y. Zhang, J. Yan, C. Lu, and X. Ni Corticotropin-releasing hormone stimulates SGK-1 kinase expression in cultured hippocampal neurons via CRH-R1 Am J Physiol Endocrinol Metab, October 1, 2008; 295(4): E938 - E946. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. E. Michael and A. T. Papageorghiou Potential significance of physiological and pharmacological glucocorticoids in early pregnancy Hum. Reprod. Update, September 1, 2008; 14(5): 497 - 517. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Estilo, W. Liu, N. Pastor-Soler, P. Mitchell, M. D. Carattino, T. R. Kleyman, and L. M. Satlin Effect of aldosterone on BK channel expression in mammalian cortical collecting duct Am J Physiol Renal Physiol, September 1, 2008; 295(3): F780 - F788. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Schuetz, S. Kumar, P. Poronnik, and D. J. Adams Regulation of the voltage-gated K+ channels KCNQ2/3 and KCNQ3/5 by serum- and glucocorticoid-regulated kinase-1 Am J Physiol Cell Physiol, July 1, 2008; 295(1): C73 - C80. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Rexhepaj, K. M. Boini, D. Y. Huang, K. Amann, F. Artunc, K. Wang, J. J. Brosens, D. Kuhl, and F. Lang Role of maternal glucocorticoid inducible kinase SGK1 in fetal programming of blood pressure in response to prenatal diet Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2008; 294(6): R2008 - R2013. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. J. McDonald A new SGK1 knockout mouse Am J Physiol Renal Physiol, June 1, 2008; 294(6): F1296 - F1297. [Full Text] [PDF] |
||||
![]() |
J. R. Bayascas, S. Wullschleger, K. Sakamoto, J. M. Garcia-Martinez, C. Clacher, D. Komander, D. M. F. van Aalten, K. M. Boini, F. Lang, C. Lipina, et al. Mutation of the PDK1 PH Domain Inhibits Protein Kinase B/Akt, Leading to Small Size and Insulin Resistance Mol. Cell. Biol., May 15, 2008; 28(10): 3258 - 3272. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. F. Arteaga, T. Coric, C. Straub, and C. M. Canessa A brain-specific SGK1 splice isoform regulates expression of ASIC1 in neurons PNAS, March 18, 2008; 105(11): 4459 - 4464. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Klaus, M. Palmada, R. Lindner, J. Laufer, S. Jeyaraj, F. Lang, and C. Boehmer Up-regulation of hypertonicity-activated myo-inositol transporter SMIT1 by the cell volume-sensitive protein kinase SGK1 J. Physiol., March 15, 2008; 586(6): 1539 - 1547. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Terada, H. Kuwana, T. Kobayashi, T. Okado, N. Suzuki, T. Yoshimoto, Y. Hirata, and S. Sasaki Aldosterone-Stimulated SGK1 Activity Mediates Profibrotic Signaling in the Mesangium J. Am. Soc. Nephrol., February 1, 2008; 19(2): 298 - 309. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Bertog, J. E. Cuffe, S. Pradervand, E. Hummler, A. Hartner, M. Porst, K. F. Hilgers, B. C. Rossier, and C. Korbmacher Aldosterone responsiveness of the epithelial sodium channel (ENaC) in colon is increased in a mouse model for Liddle's syndrome J. Physiol., January 15, 2008; 586(2): 459 - 475. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. D. Nath, V. S. Voruganti, N. H. Arar, F. Thameem, J. C. Lopez-Alvarenga, R. Bauer, J. Blangero, J. W. MacCluer, A. G. Comuzzie, and H. E. Abboud Genome Scan for Determinants of Serum Uric Acid Variability J. Am. Soc. Nephrol., December 1, 2007; 18(12): 3156 - 3163. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Li, C. S. Wingo, and S.-L. Xia Downregulation of SGK1 by nucleotides in renal tubular epithelial cells Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1751 - F1757. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Nagase, H. Matsui, S. Shibata, T. Gotoda, and T. Fujita Salt-Induced Nephropathy in Obese Spontaneously Hypertensive Rats Via Paradoxical Activation of the Mineralocorticoid Receptor: Role of Oxidative Stress Hypertension, November 1, 2007; 50(5): 877 - 883. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Feroze-Zaidi, L. Fusi, M. Takano, J. Higham, M. S. Salker, T. Goto, S. Edassery, K. Klingel, K. M. Boini, M. Palmada, et al. Role and Regulation of the Serum- and Glucocorticoid-Regulated Kinase 1 in Fertile and Infertile Human Endometrium Endocrinology, October 1, 2007; 148(10): 5020 - 5029. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. O. Wielputz, I.-H. Lee, A. Dinudom, S. Boulkroun, N. Farman, D. I. Cook, C. Korbmacher, and R. Rauh (NDRG2) Stimulates Amiloride-sensitive Na+ Currents in Xenopus laevis Oocytes and Fisher Rat Thyroid Cells J. Biol. Chem., September 21, 2007; 282(38): 28264 - 28273. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. F. Arteaga, D. Alvarez de la Rosa, J. A. Alvarez, and C. M. Canessa Multiple Translational Isoforms Give Functional Specificity to Serum- and Glucocorticoid-induced Kinase 1 Mol. Biol. Cell, June 1, 2007; 18(6): 2072 - 2080. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Seebohm, N. Strutz-Seebohm, R. Birkin, G. Dell, C. Bucci, M. R. Spinosa, R. Baltaev, A. F. Mack, G. Korniychuk, A. Choudhury, et al. Regulation of Endocytic Recycling of KCNQ1/KCNE1 Potassium Channels Circ. Res., March 16, 2007; 100(5): 686 - 692. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |