Hara Hiromitsu, Saito Takashi
Department of Biomolecular Sciences, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Trends Immunol. 2009 May;30(5):234-42. doi: 10.1016/j.it.2009.03.002. Epub 2009 Apr 7.
Nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinases (MAPKs) are activated upon engagement of a wide variety of immunoreceptors. Accumulating evidence has demonstrated that B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue (MALT1) are essential signaling components for NF-kappaB and MAPK activation mediated by immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptors in both adaptive and innate immunity. Recent studies have revealed that two caspase-recruitment domain (CARD) family adaptor molecules, CARD-containing MAGUK protein 1 (CARMA1) and CARD9, are crucial regulators of the ITAM-mediated signaling pathway by forming a complex with BCL10-MALT1 in lymphoid and myeloid cells, respectively. Here, we describe the immune responses and the cell-type-specific regulation mechanisms for NF-kappaB and MAPK activation controlled by CARMA1 and CARD9 through innate and adaptive immunoreceptors.
核因子-κB(NF-κB)和丝裂原活化蛋白激酶(MAPK)在多种免疫受体激活后被激活。越来越多的证据表明,B细胞淋巴瘤10(BCL10)和黏膜相关淋巴组织(MALT1)是适应性免疫和固有免疫中基于免疫受体酪氨酸的激活基序(ITAM)偶联受体介导的NF-κB和MAPK激活的重要信号成分。最近的研究表明,两个半胱天冬酶募集结构域(CARD)家族衔接分子,含CARD的膜相关鸟苷酸激酶蛋白1(CARMA1)和CARD9,分别通过在淋巴细胞和髓细胞中与BCL10-MALT1形成复合物,成为ITAM介导的信号通路的关键调节因子。在此,我们描述了通过固有免疫和适应性免疫受体由CARMA1和CARD9控制的NF-κB和MAPK激活的免疫反应及细胞类型特异性调节机制。