The B cell antigen receptor (BCR)–mediated activation of IκB kinase (IKK) and nuclear factor–κB require protein kinase C (PKC)β; however, the mechanism by which PKCβ regulates IKK is unclear. Here, we demonstrate that another protein kinase, TGFβ-activated kinase (TAK)1, is essential for IKK activation in response to BCR stimulation. TAK1 interacts with the phosphorylated CARMA1 (also known as caspase recruitment domain [CARD]11, Bimp3) and this interaction is mediated by PKCβ. IKK is also recruited to the CARMA1–Bcl10–mucosal-associated lymphoid tissue 1 adaptor complex in a PKCβ-dependent manner. Hence, our data suggest that phosphorylation of CARMA1, mediated by PKCβ, brings two key protein kinases, TAK1 and IKK, into close proximity, thereby allowing TAK1 to phosphorylate IKK.
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21 November 2005
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November 21 2005
PKCβ regulates BCR-mediated IKK activation by facilitating the interaction between TAK1 and CARMA1
Hisaaki Shinohara,
Hisaaki Shinohara
1Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
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Tomoharu Yasuda,
Tomoharu Yasuda
1Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
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Yuichi Aiba,
Yuichi Aiba
1Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
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Hideki Sanjo,
Hideki Sanjo
1Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
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Megumi Hamadate,
Megumi Hamadate
1Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
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Hiroshi Watarai,
Hiroshi Watarai
2Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
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Hiroaki Sakurai,
Hiroaki Sakurai
3Division of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan
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Tomohiro Kurosaki
Tomohiro Kurosaki
1Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
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Hisaaki Shinohara
1Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
Tomoharu Yasuda
1Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
Yuichi Aiba
1Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
Hideki Sanjo
1Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
Megumi Hamadate
1Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
Hiroshi Watarai
2Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
Hiroaki Sakurai
3Division of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan
Tomohiro Kurosaki
1Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
CORRESPONDENCE Tomohiro Kurosaki: [email protected]
Abbreviations used: Ab, antibody; BCR, B cell antigen receptor; CARD, caspase recruitment domain; CARMA1, caspase recruitment domain [CARD]11, Bimp3; EMSA, electrophoretic mobility shift assay; ERK, extracellular signal–regulated kinase; GST, glutathione S-transferase; IKK, IκB kinase; JNK, c-Jun NH2-terminal kinase; MAGUK, membrane-associated guanylate kinase; MALT, mucosal- associated lymphoid tissue; MAP, mitogen-activated protein; PKC, protein kinase C; TAK, TGFβ-activated kinase.
Received:
August 05 2005
Accepted:
September 13 2005
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2005
J Exp Med (2005) 202 (10): 1423–1431.
Article history
Received:
August 05 2005
Accepted:
September 13 2005
Citation
Hisaaki Shinohara, Tomoharu Yasuda, Yuichi Aiba, Hideki Sanjo, Megumi Hamadate, Hiroshi Watarai, Hiroaki Sakurai, Tomohiro Kurosaki; PKCβ regulates BCR-mediated IKK activation by facilitating the interaction between TAK1 and CARMA1 . J Exp Med 21 November 2005; 202 (10): 1423–1431. doi: https://doi.org/10.1084/jem.20051591
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