{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T02:38:31Z","timestamp":1789353511501,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":1338,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2005,6]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>In this study, we examined the role of Ca<jats:sup>2+<\/jats:sup> in linking proteinase\u2010activated receptor\u20102 (PAR2) to the nuclear factor kappa B (NF<jats:italic>\u03ba<\/jats:italic>B) pathway in a skin epithelial cell line NCTC2544 stably expressing PAR2 (clone G).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In clone G, PAR2\u2010mediated NF<jats:italic>\u03ba<\/jats:italic>B luciferase reporter activity and NF<jats:italic>\u03ba<\/jats:italic>B DNA\u2010binding activity was reduced by preincubation with BAPTA\u2010AM but not BAPTA. Trypsin stimulation of inhibitory kappa B kinases, IKK<jats:italic>\u03b1<\/jats:italic> and IKK<jats:italic>\u03b2<\/jats:italic>, was also inhibited following pretreatment with BAPTA\u2010AM.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>BAPTA\/AM also prevented PAR2\u2010mediated IKK<jats:italic>\u03b1<\/jats:italic> activation in cultured primary human keratinocytes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The effect of BAPTA\u2010AM was also selective for the IKK\/NF<jats:italic>\u03ba<\/jats:italic>B signalling axis; PAR2 coupling to ERK, or p38 MAP kinase was unaffected.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Pharmacological inhibition of the Ca<jats:sup>2+<\/jats:sup>\u2010dependent regulatory protein calcineurin did not inhibit trypsin\u2010stimulated IKK activity or NF<jats:italic>\u03ba<\/jats:italic>B\u2010DNA binding; however, inhibition of Ca<jats:sup>2+<\/jats:sup>\u2010dependent protein kinase C isoforms or InsP<jats:sub>3<\/jats:sub> formation using GF109203X or the phospholipase C inhibitor U73122, respectively, reduced both IKK activity and NF<jats:italic>\u03ba<\/jats:italic>B\u2010DNA binding.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Mutation of PAR2 within the C\u2010terminal to produce a mutant receptor, which does not couple to Ca<jats:sup>2+<\/jats:sup> signalling, but is able to activate ERK, abrogated NF<jats:italic>\u03ba<\/jats:italic>B\u2010DNA binding and IKK activity stimulated by trypsin.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results suggest a predominant role for the InsP<jats:sub>3<\/jats:sub>\/Ca<jats:sup>2+<\/jats:sup> axis in the regulation of IKK signalling and NF<jats:italic>\u03ba<\/jats:italic>B transcriptional activation.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2005) <jats:bold>145<\/jats:bold>, 535\u2013544. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706204\">10.1038\/sj.bjp.0706204<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0706204","type":"journal-article","created":{"date-parts":[[2005,4,11]],"date-time":"2005-04-11T09:32:54Z","timestamp":1113211974000},"page":"535-544","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["The role of intracellular Ca<sup>2+<\/sup> in the regulation of proteinase\u2010activated receptor\u20102 mediated nuclear factor kappa B signalling in keratinocytes"],"prefix":"10.1111","volume":"145","author":[{"given":"Scott R","family":"Macfarlane","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Callum M","family":"Sloss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Cameron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Kanke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick C","family":"McKenzie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Plevin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2002.01709.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0898-6568(02)00120-1"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01648"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200211104"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3141009"},{"key":"e_1_2_7_7_1","first-page":"5519","article-title":"Activation of protease\u2010activated receptor\u20102 (PAR\u20102) elicits nitric oxide\u2010dependent dilatation of the basilar artery in vivo","volume":"12","author":"COCKS T.M.","year":"1998","journal-title":"FASEB J."},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119658"},{"key":"e_1_2_7_9_1","first-page":"671","article-title":"Cardiovascular responses mediated by protease\u2010activated receptor\u20102 (PAR\u20102) and thrombin receptor (PAR\u20101) are distinguished in mice deficient in PAR\u20102 or PAR\u20101","volume":"288","author":"DAMIANO B.P.","year":"1999","journal-title":"J. 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