Stimulation of Ca2+-channel Orai1/STIM1 by serum- and glucocorticoid-inducible kinase 1 (SGK1).
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Stimulation of Ca2+-channel Orai1/STIM1 by serum- and glucocorticoid-inducible kinase 1 (SGK1). / Eylenstein, Anja; Gehring, Eva-Maria; Heise, Nicole; Shumilina, Ekaterina; Schmidt, Sebastian; Szteyn, Kalina; Münzer, Patrick; Nurbaeva, Meerim K; Eichenmüller, Melanie; Tyan, Leonid; Regel, Ivonne; Föller, Michael; Kuhl, Dietmar; Soboloff, Jonathan; Penner, Reinhold; Lang, Florian.
in: FASEB J, Jahrgang 25, Nr. 6, 6, 2011, S. 2012-2021.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Stimulation of Ca2+-channel Orai1/STIM1 by serum- and glucocorticoid-inducible kinase 1 (SGK1).
AU - Eylenstein, Anja
AU - Gehring, Eva-Maria
AU - Heise, Nicole
AU - Shumilina, Ekaterina
AU - Schmidt, Sebastian
AU - Szteyn, Kalina
AU - Münzer, Patrick
AU - Nurbaeva, Meerim K
AU - Eichenmüller, Melanie
AU - Tyan, Leonid
AU - Regel, Ivonne
AU - Föller, Michael
AU - Kuhl, Dietmar
AU - Soboloff, Jonathan
AU - Penner, Reinhold
AU - Lang, Florian
PY - 2011
Y1 - 2011
N2 - 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 ?M) 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.
AB - 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 ?M) 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.
KW - Animals
KW - Humans
KW - Male
KW - Female
KW - Mice
KW - Mice, Knockout
KW - Cell Movement
KW - Cell Line
KW - Gene Expression Regulation/physiology
KW - Membrane Proteins/genetics/metabolism
KW - Calcium Channels/genetics/metabolism
KW - Immediate-Early Proteins/genetics/metabolism
KW - Protein-Serine-Threonine Kinases/genetics/metabolism
KW - Calcium Signaling/physiology
KW - Neoplasm Proteins/genetics/metabolism
KW - Animals
KW - Humans
KW - Male
KW - Female
KW - Mice
KW - Mice, Knockout
KW - Cell Movement
KW - Cell Line
KW - Gene Expression Regulation/physiology
KW - Membrane Proteins/genetics/metabolism
KW - Calcium Channels/genetics/metabolism
KW - Immediate-Early Proteins/genetics/metabolism
KW - Protein-Serine-Threonine Kinases/genetics/metabolism
KW - Calcium Signaling/physiology
KW - Neoplasm Proteins/genetics/metabolism
M3 - SCORING: Journal article
VL - 25
SP - 2012
EP - 2021
JO - FASEB J
JF - FASEB J
SN - 0892-6638
IS - 6
M1 - 6
ER -
