CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-κB activation
CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-κB activation
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DOI：
10.1038/ni830
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发表时间：
2002-09-01
影响因子：
30.5
通讯作者：
Thome, M
中科院分区：
文献类型：
--
作者：
Gaide, O;Favier, B;Thome, M
CARMA 1是支架蛋白的膜相关鸟苷酸激酶（MAGUK）家族的淋巴细胞特异性成员，其协调从质膜发出的信号传导途径。CARMA 1通过其半胱天冬酶募集结构域（CARD）与Bcl 10相互作用。在这里，我们研究了CARMA 1在T细胞活化中的作用，发现T细胞受体（TCR）刺激诱导CARMA 1与TCR和Bcl 10的物理缔合。我们发现CARMA 1与脂筏组成性相关，而细胞质Bcl 10在TCR接合后易位到脂筏中。当TCR与CD 28结合时，Bcl 10结合缺陷的CARMA 1突变体对TCR诱导的NF-κ B活化和IL-2产生以及对c-Jun NH 2-末端激酶（Jnk）通路具有显性负（DN）效应。总之，我们的数据表明CARMA 1是TCR诱导的NF-κ B活化和CD 28共刺激依赖性JNK活化的关键脂筏相关调节因子。
CARMA1 is a lymphocyte-specific member of the membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins, which coordinate signaling pathways emanating from the plasma membrane. CARMA1 interacts with Bcl10 via its caspase-recruitment domain (CARD). Here we investigated the role of CARMA1 in T cell activation and found that T cell receptor (TCR) stimulation induced a physical association of CARMA1 with the TCR and Bcl10. We found that CARMA1 was constitutively associated with lipid rafts, whereas cytoplasmic Bcl10 translocated into lipid rafts upon TCR engagement. A CARMA1 mutant, defective for Bcl10 binding, had a dominant-negative (DN) effect on TCR-induced NF-kappaB activation and IL-2 production and on the c-Jun NH2-terminal kinase (Jnk) pathway when the TCR was coengaged with CD28. Together, our data show that CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappaB activation and CD28 costimulation-dependent Jnk activation.