Redox-sensitive transactivation of epidermal growth factor receptor by tumor necrosis factor confers the NF-κB activation
Redox-sensitive transactivation of epidermal growth factor receptor by tumor necrosis factor confers the NF-κB activation
复制标题
DOI：
10.1074/jbc.m011021200
复制
发表时间：
2001-07-13
影响因子：
4.8
通讯作者：
Fukuda, K
中科院分区：
文献类型：
--
作者：
Hirota, K;Murata, M;Fukuda, K
不同信号系统之间的交叉通信允许细胞在不同生理情况下接收到的多种刺激的整合。本文探讨了肿瘤坏死因子（TNF）受体信号与表皮生长因子（EGF）受体信号在核因子- κ b （nf - κ b）激活通路上相互作用的可能性。我们已经证明，即使没有EGF， NIH3T3细胞中EGF受体（EGFR）的过表达也显著增强了tnf诱导的nf - kappab依赖性荧光素酶活性，EGF处理对报告活性的诱导具有协同作用，并且这种增强被EGFR特异性酪氨酸激酶抑制剂AG1478抑制。我们还表明，TNF诱导酪氨酸磷酸化和NIH3T3细胞中过表达的EGFR的内化，以及A431细胞中内源性表达的EGFR，并且TNF的反活化被n -乙酰- l-半胱氨酸或内源性还原分子硫氧还蛋白的过表达抑制，但不被磷脂酰肌醇3-激酶抑制剂和蛋白激酶C抑制剂抑制。综上所述，这一证据强烈表明，以氧化还原依赖性方式调节的TNF对EGFR的反活化在TNF诱导的NF-kappaB活化中起着关键作用。
Cross-communication between different signaling systems allows the integration of the great diversity of stimuli that a cell receives under varying physiological situations. In this paper we have explored the possibility that tumor necrosis factor (TNF) receptor signal cross-talks with epidermal growth factor (EGF) receptor signal on the nuclear factor-kappaB (NF-kappaB) activation pathway. We have demonstrated that overexpression of the EGF receptor (EGFR) in NIH3T3 cells significantly enhances TNF-induced NF-kappaB-dependent luciferase activity even without EGF, that EGF treatment has a synergistic effect on the induction of the reporter activity, and that this enhancement is suppressed by AG1478, EGFR-specific tyrosine kinase inhibitor. We also have shown that TNF induces tyrosine phosphorylation and internalization of the overexpressed EGFR in NIH3T3 cells and the endogenously expressed EGFR in A431 cells and that the transactivation by TNF is suppressed by N-acetyl-L-cysteine or overexpression of an endogenous reducing molecule, thioredoxin, but not by phosphatidylinositol 3-kinase inhibitors and protein kinase C inhibitor. Taken together, this evidence strongly suggests that EGFR transactivation by TNF, which is regulated in a redox-dependent manner, is playing a pivotal role in TNF-induced NF-kappaB activation.