{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:02:57Z","timestamp":1791306177867,"version":"4.3.1"},"reference-count":25,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5718","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2005,4]]},"abstract":"<jats:p>Activation of the transcription factor NF-\u03baB after engagement of the T cell receptor (TCR) is important for T cell proliferation and activation during the adaptive immune response. Recent reports have elucidated a signaling pathway that involves the protein kinase C \u03b8 (PKC\u03b8), the scaffold protein CARD11 (also called CARMA-1), the caspase recruitment domain (CARD)\u2013containing protein Bcl10, and the paracaspase (protease related to caspases) MALT1 as critical intermediates linking the TCR to the I\u03baB kinase (IKK) complex. However, the events proximal to the TCR that initiate the activation of this signaling pathway remain poorly defined. We demonstrate that 3-phosphoinositide-dependent kinase 1 (PDK1) has an essential role in this pathway by regulating the activation of PKC\u03b8 and through signal-dependent recruiting of both PKC\u03b8 and CARD11 to lipid rafts. PDK1-associated PKC\u03b8 recruits the IKK complex, whereas PDK1-associated CARD11 recruits the Bcl10-MALT1 complex, thereby allowing activation of the IKK complex through Bcl10-MALT1\u2013dependent ubiquitination of the IKK complex subunit known as NEMO (NF-\u03baB essential modifier). Hence, PDK1 plays a critical role by nucleating the TCR-induced NF-\u03baB activation pathway in T cells.<\/jats:p>","DOI":"10.1126\/science.1107107","type":"journal-article","created":{"date-parts":[[2005,3,31]],"date-time":"2005-03-31T16:33:03Z","timestamp":1112286783000},"page":"114-118","source":"Crossref","is-referenced-by-count":206,"title":["PDK1 Nucleates T Cell Receptor-Induced Signaling Complex for NF-\u03baB Activation"],"prefix":"10.1126","volume":"308","author":[{"given":"Ki-Young","family":"Lee","sequence":"first","affiliation":[{"name":"Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulvio","family":"D'Acquisto","sequence":"additional","affiliation":[{"name":"Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew S.","family":"Hayden","sequence":"additional","affiliation":[{"name":"Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Hyuck","family":"Shim","sequence":"additional","affiliation":[{"name":"Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sankar","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(02)02264-0"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1228704"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.16.1.225"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.621"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00703-1"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5484.1550"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.1.164-171.2003"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.8.2933-2940.2000"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.12.6933"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1352"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02273"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5385.2042"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni848"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni847"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568009043333032"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1062"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)01073-1"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1068999"},{"key":"e_1_3_1_20_2","unstructured":"Materials and methods are available as supporting material on Science Online."},{"key":"e_1_3_1_21_2","unstructured":"K. -Y. Lee S. Ghosh unpublished results."},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf505"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00801-0"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020234"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(03)00491-3"},{"key":"e_1_3_1_26_2","unstructured":"Supported by NIH (R37-AI33443). We would like to thank J. Pober X. H. Sun and D. Rothstein for carefully reading the manuscript and X. Lin (University of Buffalo) for sharing the CARD11-deficient Jurkat cells. Molecular interaction data have been deposited in the Biomolecular Interaction Network Database with accession codes 209039 to 209044."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1107107","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T23:02:08Z","timestamp":1704841328000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1107107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,4]]},"references-count":25,"journal-issue":{"issue":"5718","published-print":{"date-parts":[[2005,4]]}},"alternative-id":["10.1126\/science.1107107"],"URL":"https:\/\/doi.org\/10.1126\/science.1107107","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1021727.298904","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1021727.295737","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,4]]}}}