Hara Hiromitsu, Bakal Christopher, Wada Teiji, Bouchard Denis, Rottapel Robert, Saito Takashi, Penninger Josef M
IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, c/o Dr. Bohr Gasse 3-5, A-1030 Vienna, Austria.
J Exp Med. 2004 Nov 1;200(9):1167-77. doi: 10.1084/jem.20032246.
Carma1 (also known as caspase recruitment domain [CARD]11, Bimp3) is a CARD-containing membrane-associated guanylate kinase family protein that plays an essential role in antigen receptor-induced nuclear factor kappaB activation. We investigated the role of Carma1 in the assembly of signaling molecules at the immune synapse using a peptide-specific system. We report that Carma1 is essential for peptide-induced interleukin 2 and interferon gamma production, but dispensable for proliferation in T cells. Recruitment and distribution of T cell receptor, lymphocyte function associated 1, lipid rafts, and protein kinase C (PKC)theta; to central and peripheral immune synapse regions occur normally in Carma1-/- T cells. Carma1 controls entry of IkappaB kinase (IKK) into lipid raft aggregates and the central region of the immune synapse, as well as activation of IKK downstream of PKC. Our data provide the first genetic evidence on a new class of molecular scaffold that controls entry of defined signaling components, IKK, into the central supramolecular activation cluster at T cell-antigen-presenting cell interfaces without having any apparent effect on the overall organization and formation of immune synapses.
Carmal（也称为胱天蛋白酶募集结构域[CARD]11、Bimp3）是一种含CARD的膜相关鸟苷酸激酶家族蛋白，在抗原受体诱导的核因子κB激活中起关键作用。我们使用肽特异性系统研究了Carmal在免疫突触处信号分子组装中的作用。我们报告称，Carmal对肽诱导的白细胞介素2和干扰素γ产生至关重要，但对T细胞增殖并非必需。T细胞受体、淋巴细胞功能相关分子1、脂筏和蛋白激酶C（PKC）θ；在Carmal基因敲除的T细胞中，它们向中央和外周免疫突触区域的募集和分布正常发生。Carmal控制IκB激酶（IKK）进入脂筏聚集体和免疫突触的中央区域，以及PKC下游的IKK激活。我们的数据提供了首个关于一类新的分子支架的遗传学证据，该支架控制特定信号成分IKK进入T细胞-抗原呈递细胞界面处的中央超分子激活簇，而对免疫突触的整体组织和形成没有任何明显影响。
