The Journal of Experimental Medicine
StemCell Technologies
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Published 21 November 2005. doi:10.1084/jem.20051591
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 10, 1423-1431
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ARTICLE

PKCß regulates BCR-mediated IKK activation by facilitating the interaction between TAK1 and CARMA1

Hisaaki Shinohara1, Tomoharu Yasuda1, Yuichi Aiba1, Hideki Sanjo1, Megumi Hamadate1, Hiroshi Watarai2, Hiroaki Sakurai3, and Tomohiro Kurosaki1

1 Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
2 Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
3 Division of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan

CORRESPONDENCE Tomohiro Kurosaki: kurosaki{at}rcai.riken.jp

The B cell antigen receptor (BCR)–mediated activation of I{kappa}B kinase (IKK) and nuclear factor–{kappa}B require protein kinase C (PKC)ß; however, the mechanism by which PKCß regulates IKK is unclear. Here, we demonstrate that another protein kinase, TGFß-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 PKCß. IKK is also recruited to the CARMA1–Bcl10–mucosal-associated lymphoid tissue 1 adaptor complex in a PKCß-dependent manner. Hence, our data suggest that phosphorylation of CARMA1, mediated by PKCß, brings two key protein kinases, TAK1 and IKK, into close proximity, thereby allowing TAK1 to phosphorylate IKK.


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, I{kappa}B 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, TGFß-activated kinase.


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