{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T22:17:07Z","timestamp":1789942627254,"version":"4.0.1"},"reference-count":48,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2006,7,26]],"date-time":"2006-07-26T00:00:00Z","timestamp":1153872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2006,8]]},"abstract":"<jats:p>Amylin\u2010mediated islet \u03b2\u2010cell death is implicated in diabetogenesis. We previously reported that fibrillogenic human amylin (hA) evokes \u03b2\u2010cell apoptosis through linked activation of Jun N\u2010terminal kinase 1 (JNK 1) and a caspase cascade. Here we show that p38 kinase [p38 mitogen\u2010activated protein (MAP) kinase] became activated by hA treatment of cultured \u03b2\u2010cells whereas extracellular signal\u2010regulated kinase (ERK) did not; by contrast, nonfibrillogenic rat amylin (rA) altered neither. Pretreatment with the p38 kinase\u2010inhibitor SB203580 decreased hA\u2010induced apoptosis and caspase\u20103 activation by \u223c30%; as did combined SB203580 and JNK inhibitor\u2003I, by about 70%; and the combination of SB203580, the JNK inhibitor\u2003I and a caspase\u20108 inhibitor, by 100%. These findings demonstrate the requirement for concurrent activation of the p38 kinase, JNK and caspase\u20108 pathways. We further showed that hA elicits time\u2010dependent activation of activating transcription factor 2 (ATF\u20102), which was largely suppressed by SB203580, indicating that this activation is catalyzed mainly by p38 kinase. Furthermore, hA\u2010induced apoptosis was suppressed by specific antisense <jats:italic>ATF\u20102<\/jats:italic>, and increased phospho\u2010ATF\u20102 (p\u2010ATF\u20102) was associated with increased <jats:italic>CRE<\/jats:italic> (cAMP\u2010response element) DNA binding and <jats:italic>CRE<\/jats:italic>\u2010mediated transcriptional activity, as well as enhancement of <jats:italic>c\u2010jun<\/jats:italic> promoter activation. We also detected changes in the phosphorylation status and composition of the CRE complex that may play important roles in regulation of distinct downstream target genes. These studies establish p38 MAP kinase\u2010mediated activation of ATF\u20102 as a significant mechanism in hA\u2010evoked \u03b2\u2010cell death, which may serve as a target for pharmaceutical intervention and effective suppression of \u03b2\u2010cell failure in type\u20102 diabetes.<\/jats:p>","DOI":"10.1111\/j.1742-4658.2006.05386.x","type":"journal-article","created":{"date-parts":[[2006,7,26]],"date-time":"2006-07-26T14:09:24Z","timestamp":1153922964000},"page":"3779-3791","source":"Crossref","is-referenced-by-count":30,"title":["Activation of activating transcription factor 2 by p38 MAP kinase during apoptosis induced by human amylin in cultured pancreatic \u03b2\u2010cells"],"prefix":"10.1111","volume":"273","author":[{"given":"Shaoping","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia A.","family":"Tse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Dragunow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garth J. S.","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,7,26]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.1.102"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-002-1009-0"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-15-2-163"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0531-5565(03)00004-4"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.9.2304"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.23.8628"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00285291"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.11.3881"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1006\/jsbi.1997.3858"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/368756a0"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/cbir.2000.0643"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0282(2001)60:6<438::AID-BIP10182>3.0.CO;2-A"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.14.7283"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1998.2299"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(02)01044-6"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)00894-7"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.8.3492"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1989"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.09.075"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.3.491"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500997200"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2005.04903.x"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M308244200"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2002.196"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.00220"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5240.1326"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)82362-6"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90403-4"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5296.90"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(01)00605-0"},{"key":"e_1_2_7_32_2","first-page":"267","article-title":"Activation of extracellular signal\u2010regulated kinase (ERK) 1\/2 contributes to cytokine\u2010induced apoptosis in purified rat pancreatic beta\u2010cells","volume":"11","author":"Pavlovic D","year":"2000","journal-title":"Eur Cytokine Network"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.26.16415"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/385350a0"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.1.188"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1989.tb03610.x"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.9.3720"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb07168.x"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(98)00275-7"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb07167.x"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200129200"},{"key":"e_1_2_7_42_2","first-page":"1","article-title":"Signal transduction by the c\u2010Jun N\u2010terminal kinase","volume":"64","author":"Davis RJ","year":"1999","journal-title":"Biochem Soc Symp"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1006\/jsbi.2000.4268"},{"key":"e_1_2_7_44_2","doi-asserted-by":"publisher","DOI":"10.1042\/0264-6021:3430053"},{"key":"e_1_2_7_45_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0405"},{"key":"e_1_2_7_46_2","first-page":"281","article-title":"In vitro growth of a cell line originated from a human insulinoma","volume":"6","author":"Gueli N","year":"1987","journal-title":"J Exp Clin Cancer Res"},{"key":"e_1_2_7_47_2","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1610059"},{"key":"e_1_2_7_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(99)00330-5"},{"key":"e_1_2_7_49_2","volume-title":"Molecular Cloning: a Laboratory Manual","author":"Sambrook J","year":"1989"}],"container-title":["The FEBS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1742-4658.2006.05386.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1742-4658.2006.05386.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T13:34:56Z","timestamp":1694784896000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1111\/j.1742-4658.2006.05386.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,7,26]]},"references-count":48,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2006,8]]}},"alternative-id":["10.1111\/j.1742-4658.2006.05386.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1742-4658.2006.05386.x","archive":["Portico"],"relation":{},"ISSN":["1742-464X","1742-4658"],"issn-type":[{"value":"1742-464X","type":"print"},{"value":"1742-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,7,26]]}}}