Wang L, Guo Y, Huang W J, Ke X, Poyet J L, Manji G A, Merriam S, Glucksmann M A, DiStefano P S, Alnemri E S, Bertin J
Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA.
J Biol Chem. 2001 Jun 15;276(24):21405-9. doi: 10.1074/jbc.M102488200. Epub 2001 Mar 20.
BCL10 belongs to the caspase recruitment domain (CARD) family of proteins that regulate apoptosis and NF-kappaB signaling pathways. Analysis of BCL10-deficient mice has revealed that BCL10 mediates NF-kappaB activation by antigen receptors in B and T cells. We recently identified a subclass of CARD proteins (CARD9, CARD11, and CARD14) that may function to connect BCL10 to multiple upstream signaling pathways. We report here that CARD10 is a novel BCL10 interactor that belongs to the membrane-associated guanylate kinase family, a class of proteins that function to organize signaling complexes at plasma membranes. When expressed in cells, CARD10 binds to BCL10 and signals the activation of NF-kappaB through its N-terminal effector CARD domain. We propose that CARD10 functions as a molecular scaffold for the assembly of a BCL10 signaling complex that activates NF-kappaB.
BCL10属于半胱天冬酶募集结构域（CARD）蛋白家族，该家族蛋白可调节细胞凋亡和核因子κB信号通路。对BCL10基因缺陷小鼠的分析表明，BCL10介导B细胞和T细胞中抗原受体对核因子κB的激活作用。我们最近鉴定出一类CARD蛋白（CARD9、CARD11和CARD14），它们可能起到将BCL10与多个上游信号通路相连接的作用。我们在此报告，CARD10是一种新型的BCL10相互作用蛋白，属于膜相关鸟苷酸激酶家族，这类蛋白的作用是在质膜上组织信号复合物。当在细胞中表达时，CARD10与BCL10结合，并通过其N端效应CARD结构域发出核因子κB激活的信号。我们提出，CARD10作为一种分子支架，用于组装激活核因子κB的BCL10信号复合物。
