A novel interaction between the juxtamembrane region of the p55 tumor necrosis factor receptor and phosphatidylinositol-4-phosphate 5-kinase
A novel interaction between the juxtamembrane region of the p55 tumor necrosis factor receptor and phosphatidylinositol-4-phosphate 5-kinase
复制标题
DOI：
10.1074/jbc.272.9.5861
复制
发表时间：
1997-02-28
影响因子：
4.8
通讯作者：
Chao, MV
中科院分区：
文献类型：
--
作者：
Castellino, AM;Parker, GJ;Chao, MV
肿瘤坏死因子-α(TNF-α)与其受体结合可导致多种生物反应。肿瘤坏死因子的作用是细胞质蛋白直接结合到两个肿瘤坏死因子受体p55和p75的胞内区的结果。在这里，我们报道了p55肿瘤坏死因子受体的膜旁区域与新发现的47 kDa的磷脂酰肌醇-4-磷酸5-激酶(PIP5K)之间的一种新的相互作用，PIP5K是产生关键信号信使磷脂酰肌醇4，5-二磷酸的酶家族的成员。这种相互作用是p55肿瘤坏死因子受体所特有的，与肿瘤坏死因子受体超家族的其他成员p75肿瘤坏死因子受体、Fas抗原或p75神经营养素受体均未观察到相互作用。使用重组融合蛋白的体外实验验证了P55受体与PIP5K的新亚型PIP5KIIβ之间相互作用的真实性，但不是先前发现的53 kDa PIP5KIIα。用肿瘤坏死因子-α处理HeLa细胞后，PIP5K活性升高。这些结果表明，磷脂酰肌醇的转换可能与P55肿瘤坏死因子受体的刺激有关，并提示PIP5KIIβ与P55肿瘤坏死因子受体的直接联系可能导致了一种亚群的肿瘤坏死因子反应。
Tumor necrosis factor-alpha (TNF-alpha) binding to its receptors leads to a diversity of biological responses. The actions of TNF are the result of the interaction of cytoplasmic proteins that bind directly to the intracellular domains of the two TNF receptors, p55 and p75. Here we report a novel interaction between the juxtamembrane region of the p55 TNF receptor and a newly discovered 47-kDa isoform of phosphatidylinositol-4-phosphate 5-kinase (PIP5K), a member of the enzyme family that generates the key signaling messenger, phosphatidylinositol 4,5-bisphosphate. The interaction was found to be specific for the p55 TNF receptor and was not observed with the p75 TNF receptor, the Fas antigen, or the p75 neurotrophin receptor, which are other members of the TNF receptor superfamily. In vitro experiments using recombinant fusion proteins verify the authenticity of the interaction between the p55 receptor and PIP5KII beta, a new isoform of PIP5K, but not the previously identified 53-kDa PIP5KII alpha. Treatment of HeLa cells with TNF-alpha resulted in an increased PIP5K activity. These results indicate that phosphatidylinositol turnover may be linked to stimulation of the p55 TNF receptor and suggest that a subset of TNF responses may result from the direct association of PIP5KII beta with the p55 TNF receptor.