Differential requirement for Malt1 in T and B cell antigen receptor signaling

被引:309
作者
Ruland, J
Duncan, GS
Wakeham, A
Mak, TW
机构
[1] Univ Toronto, Ontario Canc Inst, Adv Med Discovery Inst, Toronto, ON M5G 2C1, Canada
[2] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2C1, Canada
[3] Univ Toronto, Dept Immunol, Toronto, ON M5G 2C1, Canada
[4] Tech Univ Munich, Dept Med 3, Klinikum Rechts Isar, D-81675 Munich, Germany
关键词
D O I
10.1016/S1074-7613(03)00293-0
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The translocation t(11;18)(q21;q21) involving MALT1 is the most common chromosomal abnormality in lymphomas of mucosa-associated lymphoid tissue. Although the paracaspase MALT1 can bind to BCL10, the physiological function of MALT1 is unknown. Using mouse models, we show that Malt1 is essential for T cell activation, proliferation, and IL-2 production in response to TCR ligation and strictly required for signal-specific NF-kappaB activation induced by the TCR but not TNF-alpha. or IL-1 signaling. Malt1 operates downstream of Bcl10, controls the catalytic activity of the canonical IKK complex, and regulates the signaling of Jnk and p38 MAP kinases. In contrast to Bcl10 disruption, however, inactivation of Malt1 has only mild effects on B cell activation and does not cause defects during neurodevelopment. Thus, Malt1 is an essential regulator of Bcl10 signaling that is differentially required depending on cellular context.
引用
收藏
页码:749 / 758
页数:10
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