钙离子/钙调蛋白依赖性蛋白激酶II是CARMA1介导的核因子κB激活的调节剂。
Ca2+/calmodulin-dependent protein kinase II is a modulator of CARMA1-mediated NF-kappaB activation.
作者信息
Ishiguro Kazuhiro, Green Todd, Rapley Joseph, Wachtel Heather, Giallourakis Cosmas, Landry Aimee, Cao Zhifang, Lu Naifang, Takafumi Ando, Goto Hidemi, Daly Mark J, Xavier Ramnik J
机构信息
Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
出版信息
Mol Cell Biol. 2006 Jul;26(14):5497-508. doi: 10.1128/MCB.02469-05.
Abstract
CARMA1 is a central regulator of NF-kappaB activation in lymphocytes. CARMA1 and Bcl10 functionally interact and control NF-kappaB signaling downstream of the T-cell receptor (TCR). Computational analysis of expression neighborhoods of CARMA1-Bcl10MALT 1 for enrichment in kinases identified calmodulin-dependent protein kinase II (CaMKII) as an important component of this pathway. Here we report that Ca(2+)/CaMKII is redistributed to the immune synapse following T-cell activation and that CaMKII is critical for NF-kappaB activation induced by TCR stimulation. Furthermore, CaMKII enhances CARMA1-induced NF-kappaB activation. Moreover, we have shown that CaMKII phosphorylates CARMA1 on Ser109 and that the phosphorylation facilitates the interaction between CARMA1 and Bcl10. These results provide a novel function for CaMKII in TCR signaling and CARMA1-induced NF-kappaB activation.
摘要
CARMA1是淋巴细胞中NF-κB激活的核心调节因子。CARMA1与Bcl10在功能上相互作用，并控制T细胞受体（TCR）下游的NF-κB信号传导。对CARMA1 - Bcl10 - MALT 1表达邻域进行激酶富集的计算分析确定钙调蛋白依赖性蛋白激酶II（CaMKII）是该信号通路的重要组成部分。在此我们报告，T细胞激活后Ca(2+)/CaMKII重新分布至免疫突触，且CaMKII对于TCR刺激诱导的NF-κB激活至关重要。此外，CaMKII增强CARMA1诱导的NF-κB激活。而且，我们已表明CaMKII使CARMA1的Ser109位点磷酸化，该磷酸化促进了CARMA1与Bcl10之间的相互作用。这些结果为CaMKII在TCR信号传导及CARMA1诱导的NF-κB激活中提供了一种新功能。
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