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Phosphorylation of STIM1 at ERK1/2 target sites modulates store-operated calcium entry

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Phosphorylation of STIM1 at ERK1/2 target sites modulates store-operated calcium entry. / Pozo-Guisado, Eulalia; Campbell, David G.; Deak, Maria; Alvarez-Barrientos, Alberto; Morrice, Nicholas A.; Alvarez, Ignacio S.; Alessi, Dario R.; Martin-Romero, Francisco Javier.

In: Journal of Cell Science, Vol. 123, No. 18, 15.09.2010, p. 3084-3093.

Research output: Contribution to journalArticle

Harvard

Pozo-Guisado, E, Campbell, DG, Deak, M, Alvarez-Barrientos, A, Morrice, NA, Alvarez, IS, Alessi, DR & Martin-Romero, FJ 2010, 'Phosphorylation of STIM1 at ERK1/2 target sites modulates store-operated calcium entry' Journal of Cell Science, vol 123, no. 18, pp. 3084-3093., 10.1242/jcs.067215

APA

Pozo-Guisado, E., Campbell, D. G., Deak, M., Alvarez-Barrientos, A., Morrice, N. A., Alvarez, I. S., ... Martin-Romero, F. J. (2010). Phosphorylation of STIM1 at ERK1/2 target sites modulates store-operated calcium entry. Journal of Cell Science, 123(18), 3084-3093. 10.1242/jcs.067215

Vancouver

Pozo-Guisado E, Campbell DG, Deak M, Alvarez-Barrientos A, Morrice NA, Alvarez IS et al. Phosphorylation of STIM1 at ERK1/2 target sites modulates store-operated calcium entry. Journal of Cell Science. 2010 Sep 15;123(18):3084-3093. Available from: 10.1242/jcs.067215

Author

Pozo-Guisado, Eulalia; Campbell, David G.; Deak, Maria; Alvarez-Barrientos, Alberto; Morrice, Nicholas A.; Alvarez, Ignacio S.; Alessi, Dario R.; Martin-Romero, Francisco Javier / Phosphorylation of STIM1 at ERK1/2 target sites modulates store-operated calcium entry.

In: Journal of Cell Science, Vol. 123, No. 18, 15.09.2010, p. 3084-3093.

Research output: Contribution to journalArticle

Bibtex - Download

@article{3fa5dd4f65e54c149dd52d4652c4c7aa,
title = "Phosphorylation of STIM1 at ERK1/2 target sites modulates store-operated calcium entry",
keywords = "STIM1, Calcium, Store-operated calcium entry, SOCE, Phosphorylation, ERK1/2",
author = "Eulalia Pozo-Guisado and Campbell, {David G.} and Maria Deak and Alberto Alvarez-Barrientos and Morrice, {Nicholas A.} and Alvarez, {Ignacio S.} and Alessi, {Dario R.} and Martin-Romero, {Francisco Javier}",
year = "2010",
doi = "10.1242/jcs.067215",
volume = "123",
number = "18",
pages = "3084--3093",
journal = "Journal of Cell Science",
issn = "0021-9533",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Phosphorylation of STIM1 at ERK1/2 target sites modulates store-operated calcium entry

A1 - Pozo-Guisado,Eulalia

A1 - Campbell,David G.

A1 - Deak,Maria

A1 - Alvarez-Barrientos,Alberto

A1 - Morrice,Nicholas A.

A1 - Alvarez,Ignacio S.

A1 - Alessi,Dario R.

A1 - Martin-Romero,Francisco Javier

AU - Pozo-Guisado,Eulalia

AU - Campbell,David G.

AU - Deak,Maria

AU - Alvarez-Barrientos,Alberto

AU - Morrice,Nicholas A.

AU - Alvarez,Ignacio S.

AU - Alessi,Dario R.

AU - Martin-Romero,Francisco Javier

PY - 2010/9/15

Y1 - 2010/9/15

N2 - <p>Store-operated calcium entry (SOCE) is an important Ca2+ entry pathway that regulates many cell functions. Upon store depletion, STIM1, a transmembrane protein located in the endoplasmic reticulum (ER), aggregates and relocates close to the plasma membrane (PM) where it activates store-operated calcium channels (SOCs). Although STIM1 was early defined as a phosphoprotein, the contribution of the phosphorylation has been elusive. In the present work, STIM1 was found to be a target of extracellular-signal-regulated kinases 1 and 2 (ERK1/2) in vitro, and we have defined the ERK1/2-phosphorylated sites on the STIM1 sequence. Using HEK293 cells stably transfected for the expression of tagged STIM1, we found that alanine substitution mutants of ERK1/2 target sites reduced SOCE significantly, suggesting that phosphorylation of these residues are required to fully accomplish SOCE. Indeed, the ERK1/2 inhibitors PD184352 and PD0325901 decreased SOCE in transfected cells. Conversely, 12-O-tetradecanoylphorbol-13-acetate, which activates ERK1/2, enhanced SOCE in cells expressing wild-type tagged STIM1, but did not potentiate Ca2+ influx in cells expressing serine to alanine mutations in ERK1/2 target sites of STIM1. Alanine substitution mutations decreased Ca2+ influx without disturbing the aggregation of STIM1 upon store depletion and without affecting the relocalization in ER-PM punctae. However, our results suggest that STIM1 phosphorylation at ERK1/2 target sites can modulate SOCE by altering STIM1 binding to SOCs, because a significant decrease in FRET efficiency was observed between alanine substitution mutants of STIM1-GFP and ORAI1-CFP.</p>

AB - <p>Store-operated calcium entry (SOCE) is an important Ca2+ entry pathway that regulates many cell functions. Upon store depletion, STIM1, a transmembrane protein located in the endoplasmic reticulum (ER), aggregates and relocates close to the plasma membrane (PM) where it activates store-operated calcium channels (SOCs). Although STIM1 was early defined as a phosphoprotein, the contribution of the phosphorylation has been elusive. In the present work, STIM1 was found to be a target of extracellular-signal-regulated kinases 1 and 2 (ERK1/2) in vitro, and we have defined the ERK1/2-phosphorylated sites on the STIM1 sequence. Using HEK293 cells stably transfected for the expression of tagged STIM1, we found that alanine substitution mutants of ERK1/2 target sites reduced SOCE significantly, suggesting that phosphorylation of these residues are required to fully accomplish SOCE. Indeed, the ERK1/2 inhibitors PD184352 and PD0325901 decreased SOCE in transfected cells. Conversely, 12-O-tetradecanoylphorbol-13-acetate, which activates ERK1/2, enhanced SOCE in cells expressing wild-type tagged STIM1, but did not potentiate Ca2+ influx in cells expressing serine to alanine mutations in ERK1/2 target sites of STIM1. Alanine substitution mutations decreased Ca2+ influx without disturbing the aggregation of STIM1 upon store depletion and without affecting the relocalization in ER-PM punctae. However, our results suggest that STIM1 phosphorylation at ERK1/2 target sites can modulate SOCE by altering STIM1 binding to SOCs, because a significant decrease in FRET efficiency was observed between alanine substitution mutants of STIM1-GFP and ORAI1-CFP.</p>

KW - STIM1

KW - Calcium

KW - Store-operated calcium entry

KW - SOCE

KW - Phosphorylation

KW - ERK1/2

U2 - 10.1242/jcs.067215

DO - 10.1242/jcs.067215

M1 - Article

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 18

VL - 123

SP - 3084

EP - 3093

ER -

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