title: TAK1 adaptor proteins, TAB2 and TAB3, link the signalosome to B-cell receptor-induced IKK activation.
abstract: Transforming growth factor-β-activated kinase (TAK)1-binding proteins (TAB) activate nuclear factor-κB by linking TAK1 to signaling molecules. We investigated the mechanisms underlying B-cell receptor (BCR) signaling in TAB2- and TAB3-deficient and TAB3 domain deletion mutant DT40 B cell lines. Loss of TAB2 and TAB3 abolished BCR-induced inhibitor of κB kinase (IKK) activation and TAK1 binding to caspase recruitment domain membrane-associated guanylate kinase protein (CARMA)1. Deletion of TAB3, coupling of ubiquitin conjugation to ER degradation, coiled-coil, and zinc finger domains blocked IKK activation and association with CARMA1. Thus, TAB2 and TAB3 connect signaling molecules that activate IKK in BCR signaling.
authors: Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa, Japan. hisaaki.shinohara@riken.jp.
authors: Hisaaki
authors: 0000-0002-6331-2138
authors: H
authors: Shinohara
authors: Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
authors: Tomoharu
authors: T
authors: Yasuda
authors: Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa, Japan.|Laboratory for Lymphocyte Differentiation, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
authors: Tomohiro
authors: T
authors: Kurosaki
mesh_terms: D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000378:metabolism; D002460:Cell Line; D002645:Chickens; D006162:Guanylate Cyclase / Q000378:metabolism; D051550:I-kappa B Kinase / Q000378:metabolism*; D057125:Nuclear Receptor Subfamily 2, Group C, Member 2 / Q000378:metabolism*; D011485:Protein Binding; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D053468:CARD Signaling Adaptor Proteins; D057125:Nuclear Receptor Subfamily 2, Group C, Member 2; D011947:Receptors, Antigen, B-Cell; D025801:Ubiquitin; D051550:I-kappa B Kinase; D006162:Guanylate Cyclase
keywords: B-cell receptor signaling; DT40 B cells; TAK1-binding protein; gene targeting; inhibitor of κB kinase; transforming growth factor -β (TGF-β)-activated kinase 1