MADD, a Novel Death Domain Protein That Interacts with the Type 1 Tumor Necrosis Factor Receptor and Activates Mitogen-activated Protein Kinase*
MADD, a Novel Death Domain Protein That Interacts with the Type 1 Tumor Necrosis Factor Receptor and Activates Mitogen-activated Protein Kinase*
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MADD，一种新型死亡结构域蛋白，可与 1 型肿瘤坏死因子受体相互作用并激活丝裂原激活蛋白激酶*
DOI：
10.1074/jbc.272.18.12069
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Lih
中科院分区：
文献类型：
--
作者：
A. Schievella;Jennifer H. Chen;J. Graham;Lih
1型肿瘤坏死因子受体（TNFR 1）的死亡结构域介导与参与TNF下游效应信号传导的几种蛋白质的相互作用。我们已经使用酵母相互作用陷阱分离蛋白质，MADD，通过其自身的C-末端死亡结构域与TNFR 1的死亡结构域相关联。MADD与TNFR 1残基相互作用，这些残基对信号产生至关重要，并与TNFR 1共免疫沉淀，暗示MADD是TNFR 1信号复合物的组分。重要的是，我们已经发现MADD的过表达激活促分裂原活化蛋白（MAP）激酶细胞外信号调节激酶（ERK），MADD死亡结构域的表达刺激ERK和c-JUN N-末端激酶MAP激酶，并诱导胞浆磷脂酶A2的磷酸化。这些数据表明MADD将TNFR 1与MAP激酶激活和花生四烯酸释放联系起来，并进一步深入了解TNF发挥其多效性作用的机制。
The death domain of the type 1 tumor necrosis factor receptor (TNFR1) mediates interactions with several proteins involved in signaling the downstream effects of TNF. We have used the yeast interaction trap to isolate a protein, MADD, that associates with the death domain of TNFR1 through its own C-terminal death domain. MADD interacts with TNFR1 residues that are critical for signal generation and coimmunoprecipitates with TNFR1, implicating MADD as a component of the TNFR1 signaling complex. Importantly, we have found that overexpression of MADD activates the mitogen-activated protein (MAP) kinase extracellular signal-regulated kinase (ERK), and expression of the MADD death domain stimulates both the ERK and c-JUN N-terminal kinase MAP kinases and induces the phosphorylation of cytosolic phospholipase A2. These data indicate that MADD links TNFR1 with MAP kinase activation and arachidonic acid release and provide further insight into the mechanisms by which TNF exerts its pleiotropic effects.
影响因子：
64.5
作者：
Muzio, M;Chinnaiyan, AM;Dixit, VM
通讯作者：
Dixit, VM