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dc.contributor.authorJans, R.*
dc.contributor.authorMottram, L.*
dc.contributor.authorJohnson, D.L.*
dc.contributor.authorBrown, A.M.*
dc.contributor.authorSikkink, Stephen K.*
dc.contributor.authorRoss, K.*
dc.contributor.authorReynolds, N.J.*
dc.date.accessioned2015-06-15T14:56:09Z
dc.date.available2015-06-15T14:56:09Z
dc.date.issued2013
dc.identifier.citationJans R, Mottram L, Johnson DL, Brown AM, Sikkink S, Ross K and Reynolds NJ (2013) Lysophosphatidic acid promotes cell migration through STIM1- and Orai1-mediated Ca2+(i) mobilization and NFAT2 activation. Journal of Investigative Dermatology. 133(3): 793-802.en_US
dc.identifier.urihttp://hdl.handle.net/10454/7256
dc.descriptionnoen_US
dc.description.abstractLysophosphatidic acid (LPA) enhances cell migration and promotes wound healing in vivo, but the intracellular signaling pathways regulating these processes remain incompletely understood. Here we investigated the involvement of agonist-induced Ca2+ entry and STIM1 and Orai1 proteins in regulating nuclear factor of activated T cell (NFAT) signaling and LPA-induced keratinocyte cell motility. As monitored by Fluo-4 imaging, stimulation with 10 μM LPA in 60 μM Ca2+o evoked Ca2+i transients owing to store release, whereas addition of LPA in physiological 1.2 mM Ca2+o triggered store release coupled to extracellular Ca2+ entry. Store-operated Ca2+ entry (SOCE) was blocked by the SOCE inhibitor diethylstilbestrol (DES), STIM1 silencing using RNA interference (RNAi), and expression of dominant/negative Orai1R91W. LPA induced significant NFAT activation as monitored by nuclear translocation of green fluorescent protein-tagged NFAT2 and a luciferase reporter assay, which was impaired by DES, expression of Orai1R91W, and inhibition of calcineurin using cyclosporin A (CsA). By using chemotactic migration assays, LPA-induced cell motility was significantly impaired by STIM1, CsA, and NFAT2 knockdown using RNAi. These data indicate that in conditions relevant to epidermal wound healing, LPA induces SOCE and NFAT activation through Orai1 channels and promotes cell migration through a calcineurin/NFAT2-dependent pathway.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.1038/jid.2012.370en_US
dc.subjectLysophosphatidic acid; LPA; Cell migration; Cell motility; STIM1- and Orai1-Mediated Ca2+i mobilization; NFAT2 activationen_US
dc.titleLysophosphatidic Acid Promotes Cell Migration through STIM1- and Orai1-Mediated Ca2+i Mobilization and NFAT2 Activationen_US
dc.status.refereedyesen_US
dc.typeArticleen_US
dc.type.versionpublished version paperen_US


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