Caveolin-1 associates with TRAF2 to form a complex that is recruited to tumor necrosis factor receptors
Caveolin-1 associates with TRAF2 to form a complex that is recruited to tumor necrosis factor receptors
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DOI：
10.1074/jbc.m007116200
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发表时间：
2001-03-16
影响因子：
4.8
通讯作者：
Pober, JS
中科院分区：
文献类型：
--
作者：
Feng, X;Gaeta, ML;Pober, JS
肿瘤坏死因子（TNF）受体相关因子（TRAF）2是一种细胞内衔接蛋白，在TNF刺激后，直接募集至TNF受体2（TNFR 2）的细胞内区域，或通过TRADD间接募集至TNF受体1（TNFR 1）的细胞内区域。在培养的人脐静脉内皮细胞中，内源性TRAF 2与膜组织蛋白小窝蛋白-1共定位在质膜下的富集区域，如通过共聚焦荧光显微镜检测到的。内源性和转染的TRAF 2蛋白在配体不存在的情况下与小窝蛋白-1共免疫沉淀。在TNF处理后，TRAF 2-小窝蛋白-1复合物与TRADD瞬时结合，并且在TNFR 2过表达后，TRAF 2-小窝蛋白-1复合物稳定地与该受体结合并引起该受体的再分布，如通过共聚焦荧光显微镜检测的。在具有最小内源性小窝蛋白-1表达的人胚肾293细胞中，TRAF 2和小窝蛋白-1的共转染导致这些蛋白质的自发结合，其可进一步与转染的TNFR 2分子结合并重新分布。Caveolin-1与TNFR 2的结合依赖于TRAF 2。小窝蛋白-1蛋白的共转染增加了HEK 293细胞中TRAF 2蛋白的表达水平，这与TNF和TRAF 2信号传导的增强相关，测量为NF-κ B启动子-报告基因的转录，尽管小窝蛋白增强的对TNF的应答在较高的小窝蛋白水平下减弱。这些发现表明，激活的TNF受体的细胞内分布可能是由小窝蛋白-1通过其与TRAF 2的相互作用进行调节。
Tumor necrosis factor (TNF) receptor-associated factor (TRAF) 2 is an intracellular adapter protein, which, upon TNF stimulation, is directly recruited to the intracellular region of TNF receptor 2 (TNFR2) or indirectly, via TRADD, to the intracellular region of TNF receptor 1 (TNFR1). In cultured human umbilical vein endothelial cells, endogenous TRAF2 colocalizes with the membrane-organizing protein caveolin-1 at regions of enrichment subjacent to the plasma membrane as detected by confocal fluorescence microscopy. Both endogenous and transfected TRAF2 protein coimmunoprecipitate with caveolin-1 in the absence of ligand. Upon TNF treatment, the TRAF2-caveolin-1 complex transiently associates with TRADD, and upon overexpression of TNFR2, the TRAF2-caveolin-1 complex stably associates with and causes redistribution of this receptor as detected by confocal fluorescence microscopy, In human embryonic kidney 293 cells, which have minimal endogenous expression of caveolin-1, cotransfection of TRAF2 and caveolin-1 results in spontaneous association of these proteins which can further associate with and redistribute transfected TNFR2 molecules. The association of caveolin-1 with TNFR2 depends upon TRAF2. Cotransfection of caveolin-1 protein increases TRAF2 protein expression levels in HEK 293 cells, which correlates with enhancement of TNF and TRAF2 signaling, measured as transcription of a NF-kappaB promoter-reporter gene, although the caveolin-enhanced response to TNF is attenuated at higher caveolin levels. These findings suggest that intracellular distribution of activated TNF receptors may be regulated by caveolin-1 via its interaction with TRAF2.