title: Bcl10 is phosphorylated on Ser138 by Ca2+/calmodulin-dependent protein kinase II.
abstract: Ordered assembly of scaffold proteins Carma1-Bcl10-Malt1 determines NF-kappaB activation following T cell receptor (TCR) engagement. Carma1-Bcl10 interaction and the signaling pathway are controlled by Carma1 phosphorylation, which are induced by PKCtheta and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). In addition to Carma1 phosphorylation, previous studies have demonstrated that Bcl10 is phosphorylated in the C-terminal Ser/Thr rich region following TCR engagement. However the kinases that phosphorylate Bcl10 are incompletely understood. Here we show that CaMKII phosphorylates Bcl10 on Ser138. Furthermore, a CaMKII inhibitor, KN93, and CaMKII siRNA substantially reduce Bcl10 phosphorylation induced by phorbol myristate acetate/ionomycin. S138A mutation prolongs Bcl10-induced NF-kappaB activation, suggesting that Bcl10 phosphorylation is involved in attenuation of NF-kappaB activation. These findings suggest that CaMKII modulates NF-kappaB activation via phosphorylating Bcl10 as well as Carma1.
authors.affiliation: Molecular Biology and Pathogenesis of Gastroenterology, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan. kio@med.nagoya-u.ac.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ishiguro
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ando
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
authors.forename: Ramnik
authors.initials: R
authors.lastname: Xavier
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000276:immunology / Q000378:metabolism; D000074018:B-Cell CLL-Lymphoma 10 Protein; D001596:Benzylamines / Q000494:pharmacology; D053468:CARD Signaling Adaptor Proteins / Q000276:immunology / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology; D020169:Caspases / Q000276:immunology / Q000378:metabolism; D006162:Guanylate Cyclase / Q000276:immunology / Q000378:metabolism; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D019169:Jurkat Cells; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D020125:Mutation, Missense; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D012694:Serine / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000074018:B-Cell CLL-Lymphoma 10 Protein; D001596:Benzylamines; D053468:CARD Signaling Adaptor Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002273:Carcinogens; D020169:Caspases; D006162:Guanylate Cyclase; D015759:Ionomycin; D007476:Ionophores; D007527:Isoenzymes; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D016328:NF-kappa B; D009363:Neoplasm Proteins; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell; D012694:Serine; D013449:Sulfonamides; D013755:Tetradecanoylphorbol Acetate; C118591:BCL10 protein, human; C072105:KN 93; D000096926:Benzenesulfonamides; C076233:PRKCQ protein, human; C400109:MALT1 protein, human; C426242:CARD11 protein, human