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dc.contributor.authorSoltoff, Stephen P.en_US
dc.contributor.authorLannon, William A.en_US
dc.date.accessioned2014-03-10T16:17:34Z
dc.date.issued2013en_US
dc.identifier.citationSoltoff, Stephen P., and William A. Lannon. 2013. “Activation of ERK1/2 by Store-Operated Calcium Entry in Rat Parotid Acinar Cells.” PLoS ONE 8 (8): e72881. doi:10.1371/journal.pone.0072881. http://dx.doi.org/10.1371/journal.pone.0072881.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11877114
dc.description.abstractThe regulation of intracellular Ca2+ concentration ([Ca2+]i) plays a critical role in a variety of cellular processes, including transcription, protein activation, vesicle trafficking, and ion movement across epithelial cells. In many cells, the activation of phospholipase C-coupled receptors hydrolyzes membrane phosphoinositides and produces the depletion of endoplasmic reticulum Ca2+ stores, followed by the sustained elevation of [Ca2+]i from Ca2+ entry across the plasma membrane via store-operated Ca2+ entry (SOCE). Ca2+ entry is also increased in a store-independent manner by arachidonate-regulated Ca2+ (ARC) channels. Using rat parotid salivary gland cells, we examined multiple pathways of Ca2+ entry/elevation to determine if they activated cell signaling proteins and whether this occurred in a pathway-dependent manner. We observed that SOCE activates extracellular signal-related kinases 1 and 2 (ERK1/2) to ∼3-times basal levels via a receptor-independent mechanism when SOCE was initiated by depleting Ca2+ stores using the endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin (TG). TG-initiated ERK1/2 phosphorylation increased as rapidly as that initiated by the muscarinic receptor agonist carbachol, which promoted an increase to ∼5-times basal levels. Notably, ERK1/2 phosphorylation was not increased by the global elevation of [Ca2+]i by Ca2+ ionophore or by Ca2+ entry via ARC channels in native cells, although ERK1/2 phosphorylation was increased by Ca2+ ionophore in Par-C10 and HSY salivary cell lines. Agents and conditions that blocked SOCE in native cells, including 2-aminoethyldiphenyl borate (2-APB), SKF96363, and removal of extracellular Ca2+, also reduced TG- and carbachol-stimulated ERK1/2 phosphorylation. TG-promoted ERK1/2 phosphorylation was blocked when SRC and Protein Kinases C (PKC) were inhibited, and it was blocked in cells pretreated with β-adrenergic agonist isoproterenol. These observations demonstrate that ERK1/2 is activated by a selective mechanism of Ca2+ entry (SOCE) in these cells, and suggest that ERK1/2 may contribute to events downstream of SOCE.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0072881en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756958/pdf/en
dash.licenseLAAen_US
dc.subjectBiologyen
dc.subjectAnatomy and Physiologyen
dc.subjectDigestive Systemen
dc.subjectDigestive Physiologyen
dc.subjectPhysiological Processesen
dc.subjectHomeostasisen
dc.subjectCell Physiologyen
dc.subjectFluid Physiologyen
dc.subjectMolecular Cell Biologyen
dc.subjectSignal Transductionen
dc.subjectSignaling Cascadesen
dc.subjectCalcium Signaling Cascadeen
dc.subjectSignaling in Cellular Processesen
dc.subjectCalcium Signalingen
dc.subjectSignaling Pathwaysen
dc.subjectCalcium-Mediated Signal Transductionen
dc.subjectMedicineen
dc.subjectOral Medicineen
dc.subjectOral Diseasesen
dc.titleActivation of ERK1/2 by Store-Operated Calcium Entry in Rat Parotid Acinar Cellsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorSoltoff, Stephen P.en_US
dc.date.available2014-03-10T16:17:34Z
dc.identifier.doi10.1371/journal.pone.0072881*
dash.contributor.affiliatedSoltoff, Stephen


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