{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T16:51:31Z","timestamp":1761843091204},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2003,10,30]],"date-time":"2003-10-30T00:00:00Z","timestamp":1067472000000},"content-version":"vor","delay-in-days":667,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European Journal of Biochemistry"],"published-print":{"date-parts":[[2002,1]]},"abstract":"<jats:p>Exposure of PC12 cells to C<jats:sub>2<\/jats:sub>\u2010ceramide results in dose\u2010dependent apoptosis. Here, we investigate the involvement of death\u2010associated protein (DAP) kinase, initially identified as a positive mediator of the interferon\u2010\u03b3\u2010induced apoptosis of HeLa cells, in the C<jats:sub>2<\/jats:sub>\u2010ceramide\u2010induced apoptosis of PC12 cells. DAP kinase is endogenously expressed in these cells. On exposure of PC12 cells to 30\u2003\u00b5<jats:sc>m<\/jats:sc> C<jats:sub>2<\/jats:sub>\u2010ceramide, both the total (assayed in the presence of Ca<jats:sup>2+<\/jats:sup>\/calmodulin) and Ca<jats:sup>2+<\/jats:sup>\/calmodulin\u2010independent (assayed in the presence of EGTA) DAP kinase activities were transiently increased 5.0\u2010 and 12.2\u2010fold, respectively, at 10\u2003min, and then decreased to 1.7\u2010 and 3.4\u2010fold at 90\u2003min. After 10\u2003min exposure to 30\u2003\u00b5<jats:sc>m<\/jats:sc> C<jats:sub>2<\/jats:sub>\u2010ceramide, the Ca<jats:sup>2+<\/jats:sup>\/calmodulin independent activity\/ total activity ratio increased from 0.22 to 0.60. These effects were dependent on the C<jats:sub>2<\/jats:sub>\u2010ceramide concentration. C<jats:sub>8<\/jats:sub>\u2010ceramide, another active ceramide analog, also induced apoptosis and activated DAP kinase, while C<jats:sub>2<\/jats:sub>\u2010dihydroceramide, an inactive ceramide analog, failed to induce apoptosis and increase DAP kinase activity. Furthermore, transfection studies revealed that overexpression of wild\u2010type DAP kinase enhanced the sensitivity to C<jats:sub>2<\/jats:sub>\u2010 and C<jats:sub>8<\/jats:sub>\u2010ceramide, while a catalytically inactive DAP kinase mutant and a construct containing the death domain and C\u2010terminal tail of DAP kinase, which act in a dominant\u2010negative manner, rescued cells from C<jats:sub>2<\/jats:sub>\u2010, and C<jats:sub>8<\/jats:sub>\u2010ceramide\u2010induced apoptosis. These findings demonstrate that DAP kinase is an important component of the apoptotic machinery involved in ceramide\u2010induced apoptosis, and that the intrinsic DAP kinase activity is critical for ceramide\u2010induced apoptosis.<\/jats:p>","DOI":"10.1046\/j.0014-2956.2002.00029.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T18:30:17Z","timestamp":1047407417000},"page":"139-147","source":"Crossref","is-referenced-by-count":48,"title":["DAP kinase activity is critical for C<sub>2<\/sub>\u2010ceramide\u2010induced apoptosis in PC12 cells"],"prefix":"10.1111","volume":"269","author":[{"given":"Mutsuya","family":"Yamamoto","sequence":"first","affiliation":[]},{"given":"Takeshi","family":"Hioki","sequence":"additional","affiliation":[]},{"given":"Takehisa","family":"Ishii","sequence":"additional","affiliation":[]},{"given":"Sadayo","family":"Nakajima\u2010Iijima","sequence":"additional","affiliation":[]},{"given":"Shigeo","family":"Uchino","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2003,10,30]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.1.15"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-419X(98)00002-X"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-4310(98)01263-5"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.5.998"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(00)89070-2"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.146.999.141"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.020519497"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19991201)58:5<674::AID-JNR8>3.3.CO;2-V"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(00)88961-6"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(96)80061-5"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.66020733.x"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19981015)54:2<206::AID-JNR8>3.0.CO;2-I"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1021008626887"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(96)01460-3"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-008303-9.50016-5"},{"key":"e_1_2_7_17_2","doi-asserted-by":"crossref","first-page":"29710","DOI":"10.1016\/S0021-9258(18)43938-5","article-title":"Mycalolide B, a novel actin depolymerizing agent","volume":"269","author":"Saito S.","year":"1994","journal-title":"J. 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