Stimulation of Ca2+-channel Orai1/STIM1 by Serum- and Glucocorticoid-inducible Kinase 1 (SGK1)

Overview

Journal FASEB J

Specialties Biology
Physiology

Date 2011 Mar 10

PMID 21385992

Citations 41

Authors

Anja Eylenstein

Eva-Maria Gehring

Nicole Heise

Ekaterina Shumilina

Sebastian Schmidt

Kalina Szteyn

Patrick Munzer

Meerim K Nurbaeva

Melanie Eichenmuller

Leonid Tyan

Ivonne Regel

Michael Foller

Dietmar Kuhl

Jonathan Soboloff

Reinhold Penner

Florian Lang

Affiliations

Soon will be listed here.

Abstract

Ca(2+) signaling includes store-operated Ca(2+) entry (SOCE) following depletion of endoplasmic reticulum (ER) Ca(2+) stores. On store depletion, the ER Ca(2+) sensor STIM1 activates Orai1, the pore-forming unit of Ca(2+)-release-activated Ca(2+) (CRAC) channels. Here, we show that Orai1 is regulated by serum- and glucocorticoid-inducible kinase 1 (SGK1), a growth factor-regulated kinase. Membrane Orai1 protein abundance, I(CRAC), and SOCE in human embryonic kidney (HEK293) cells stably expressing Orai1 and transfected with STIM1 were each significantly enhanced by coexpression of constitutively active (S422D)SGK1 (by+81, +378, and+136%, respectively) but not by inactive (K127N)SGK1. Coexpression of the ubiquitin ligase Nedd4-2, an established negatively regulated SGK1 target, down-regulated SOCE (by -48%) and I(CRAC) (by -60%), an effect reversed by expression of (S422D)SGK1 (by +175 and +173%, respectively). Orai1 protein abundance and SOCE were significantly lower in mast cells from SGK1-knockout (sgk1(-/-)) mice (by -37% and -52%, respectively) than in mast cells from wild-type (sgk1(+/+)) littermates. Activation of SOCE by sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase-inhibitor thapsigargin (2 μM) stimulated migration, an effect significantly higher (by +306%) in (S422D)SGK1-expressing than in (K127N)SGK1-expressing HEK293 cells, and also significantly higher (by +108%) in sgk1(+/+) than in sgk1(-/-) mast cells. SGK1 is thus a novel key player in the regulation of SOCE.

Citing Articles

Exploring the pathophysiological mechanisms and wet biomarkers of disease.

Lin J, Meng H, Shafeng N, Li J, Sun H, Yang X Front Neurol. 2024; 15:1482936.

PMID: 39659962 PMC: 11628379. DOI: 10.3389/fneur.2024.1482936.

STIM1 in tumor cell death: angel or devil?.

Ren R, Li Y Cell Death Discov. 2023; 9(1):408.

PMID: 37932320 PMC: 10628139. DOI: 10.1038/s41420-023-01703-8.

Beyond Corticoresistance, A Paradoxical Corticosensitivity Induced by Corticosteroid Therapy in Pediatric Acute Lymphoblastic Leukemias.

Angot L, Schneider P, Vannier J, Abdoul-Azize S Cancers (Basel). 2023; 15(10).

PMID: 37345151 PMC: 10216755. DOI: 10.3390/cancers15102812.

Cortisol Rapidly Facilitates Glucocorticoid Receptor Translocation to the Plasma Membrane in Primary Trout Hepatocytes.

Das C, Vijayan M Biology (Basel). 2023; 12(2).

PMID: 36829586 PMC: 9953755. DOI: 10.3390/biology12020311.

AKT Regulation of ORAI1-Mediated Calcium Influx in Breast Cancer Cells.

Bong A, Hua T, So C, Peters A, Robitaille M, Tan Y Cancers (Basel). 2022; 14(19).

PMID: 36230716 PMC: 9562175. DOI: 10.3390/cancers14194794.

References

Rotte A, Bhandaru M, Foller M, Biswas R, Mack A, Friedrich B . APC sensitive gastric acid secretion. Cell Physiol Biochem. 2009; 23(1-3):133-42. DOI: 10.1159/000204102. View

Bohmer C, Palmada M, Kenngott C, Lindner R, Klaus F, Laufer J . Regulation of the epithelial calcium channel TRPV6 by the serum and glucocorticoid-inducible kinase isoforms SGK1 and SGK3. FEBS Lett. 2007; 581(29):5586-90. DOI: 10.1016/j.febslet.2007.11.006. View

Baryshnikov S, Pulina M, Zulian A, Linde C, Golovina V . Orai1, a critical component of store-operated Ca2+ entry, is functionally associated with Na+/Ca2+ exchanger and plasma membrane Ca2+ pump in proliferating human arterial myocytes. Am J Physiol Cell Physiol. 2009; 297(5):C1103-12. PMC: 2777402. DOI: 10.1152/ajpcell.00283.2009. View

Becchetti A, Arcangeli A . Integrins and ion channels in cell migration: implications for neuronal development, wound healing and metastatic spread. Adv Exp Med Biol. 2010; 674:107-23. DOI: 10.1007/978-1-4419-6066-5_10. View

Bhalla V, Soundararajan R, Pao A, Li H, Pearce D . Disinhibitory pathways for control of sodium transport: regulation of ENaC by SGK1 and GILZ. Am J Physiol Renal Physiol. 2006; 291(4):F714-21. DOI: 10.1152/ajprenal.00061.2006. View

Pani B, Singh B . Lipid rafts/caveolae as microdomains of calcium signaling. Cell Calcium. 2009; 45(6):625-33. PMC: 2695836. DOI: 10.1016/j.ceca.2009.02.009. View

Ji W, Xu P, Li Z, Lu J, Liu L, Zhan Y . Functional stoichiometry of the unitary calcium-release-activated calcium channel. Proc Natl Acad Sci U S A. 2008; 105(36):13668-73. PMC: 2533247. DOI: 10.1073/pnas.0806499105. View

Wang K, Gu S, Nasir O, Foller M, Ackermann T, Klingel K . SGK1-dependent intestinal tumor growth in APC-deficient mice. Cell Physiol Biochem. 2010; 25(2-3):271-8. DOI: 10.1159/000276561. View

Yeromin A, Zhang S, Jiang W, Yu Y, Safrina O, Cahalan M . Molecular identification of the CRAC channel by altered ion selectivity in a mutant of Orai. Nature. 2006; 443(7108):226-9. PMC: 2756048. DOI: 10.1038/nature05108. View

10.

Sherk A, Frigo D, Schnackenberg C, Bray J, Laping N, Trizna W . Development of a small-molecule serum- and glucocorticoid-regulated kinase-1 antagonist and its evaluation as a prostate cancer therapeutic. Cancer Res. 2008; 68(18):7475-83. PMC: 2562281. DOI: 10.1158/0008-5472.CAN-08-1047. View

11.

Liang X, Peters K, Butterworth M, Frizzell R . 14-3-3 isoforms are induced by aldosterone and participate in its regulation of epithelial sodium channels. J Biol Chem. 2006; 281(24):16323-32. DOI: 10.1074/jbc.M601360200. View

12.

Bradding P, Wulff H . The K+ channels K(Ca)3.1 and K(v)1.3 as novel targets for asthma therapy. Br J Pharmacol. 2009; 157(8):1330-9. PMC: 2765317. DOI: 10.1111/j.1476-5381.2009.00362.x. View

13.

Debonneville C, Flores S, Kamynina E, Plant P, Tauxe C, Thomas M . Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression. EMBO J. 2001; 20(24):7052-9. PMC: 125341. DOI: 10.1093/emboj/20.24.7052. View

14.

Vig M, DeHaven W, Bird G, Billingsley J, Wang H, Rao P . Defective mast cell effector functions in mice lacking the CRACM1 pore subunit of store-operated calcium release-activated calcium channels. Nat Immunol. 2007; 9(1):89-96. PMC: 2377025. DOI: 10.1038/ni1550. View

15.

Krueger B, Haerteis S, Yang L, Hartner A, Rauh R, Korbmacher C . Cholesterol depletion of the plasma membrane prevents activation of the epithelial sodium channel (ENaC) by SGK1. Cell Physiol Biochem. 2009; 24(5-6):605-18. DOI: 10.1159/000257516. View

16.

Embark H, Setiawan I, Poppendieck S, van de Graaf S, Boehmer C, Palmada M . Regulation of the epithelial Ca2+ channel TRPV5 by the NHE regulating factor NHERF2 and the serum and glucocorticoid inducible kinase isoforms SGK1 and SGK3 expressed in Xenopus oocytes. Cell Physiol Biochem. 2004; 14(4-6):203-12. DOI: 10.1159/000080329. View

17.

Schaff U, Dixit N, Procyk E, Yamayoshi I, Tse T, Simon S . Orai1 regulates intracellular calcium, arrest, and shape polarization during neutrophil recruitment in shear flow. Blood. 2009; 115(3):657-66. PMC: 2810981. DOI: 10.1182/blood-2009-05-224659. View

18.

Shin D, Muallem S . Skeletal muscle dressed in SOCs. Nat Cell Biol. 2008; 10(6):639-41. DOI: 10.1038/ncb0608-639. View

19.

Palmada M, Poppendieck S, Embark H, van de Graaf S, Boehmer C, Bindels R . Requirement of PDZ domains for the stimulation of the epithelial Ca2+ channel TRPV5 by the NHE regulating factor NHERF2 and the serum and glucocorticoid inducible kinase SGK1. Cell Physiol Biochem. 2005; 15(1-4):175-82. DOI: 10.1159/000083650. View

20.

Peinelt C, Vig M, Koomoa D, Beck A, Nadler M, Koblan-Huberson M . Amplification of CRAC current by STIM1 and CRACM1 (Orai1). Nat Cell Biol. 2006; 8(7):771-3. PMC: 5685802. DOI: 10.1038/ncb1435. View