Lysophosphatidic acid promotes cell migration through STIM1- and Orai1-mediated Ca2+(i) mobilization and NFAT2 activation.

ABSTRACT: Lysophosphatidic 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 Ca(2+) 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 Ca(2+)(o) evoked Ca(2+)(i) transients owing to store release, whereas addition of LPA in physiological 1.2 mM Ca(2+)(o) triggered store release coupled to extracellular Ca(2+) entry. Store-operated Ca(2+) entry (SOCE) was blocked by the SOCE inhibitor diethylstilbestrol (DES), STIM1 silencing using RNA interference (RNAi), and express

SUBMITTER: Jans R 

PROVIDER: S-EPMC3572452 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature