The atypical protein kinase C-interacting protein p62 is a scaffold for NF-κB activation by nerve growth factor
The atypical protein kinase C-interacting protein p62 is a scaffold for NF-κB activation by nerve growth factor
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DOI：
10.1074/jbc.c000869200
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发表时间：
2001-03-16
影响因子：
4.8
通讯作者：
Moscat, J
中科院分区：
文献类型：
--
作者：
Wooten, MW;Seibenhener, ML;Moscat, J
神经生长因子 (NGF) 与 p75 和 TrkA 神经营养素受体结合可激活转录因子核因子 kappaB (NF-kappaB)。在这里，我们表明非典型蛋白激酶 C 相互作用蛋白 p62 与 TRAF6 结合，选择性地与 TrkA 相互作用，但不与 p75 相互作用。相比之下，TRAF6 与 p75 相互作用，但不与 TrkA 相互作用。我们证明了 TRAF6-p62 复合物的形成，该复合物充当连接 p75 和 TrkA 信号传导的桥梁。与功能相关的是，反义 p62 的转染增强了 p75 介导的细胞死亡并减少了 NGF 诱导的分化，这是通过抑制 IKK 活性的机制发生的。这些发现揭示了 p62 作为 p75-TRAF6 和 TrkA 信号通信的通用平台的新功能。此外，我们证明 p62 可作为 NF-kappaB 通路激活的支架，介导 NGF 存活和分化反应。
Nerve growth factor (NGF) binding to both p75 and TrkA neurotrophin receptors activates the transcription factor nuclear factor kappaB (NF-kappaB). Here we show that the atypical protein kinase C-interacting protein, p62, which binds TRAF6, selectively interacts with TrkA but not p75. In contrast, TRAF6 interacts with p75 but not TrkA. We demonstrate the formation of a TRAF6-p62 complex that serves as a bridge linking both p75 and TrkA signaling. Of functional relevance, transfection of antisense p62-enhanced p75-mediated cell death and diminished NGF-induced differentiation occur through a mechanism involving inhibition of IKK activity. These findings reveal a new function for p62 as a common platform for communication of both p75-TRAF6 and TrkA signals. Moreover, we demonstrated that p62 serves as a scaffold for activation of the NF-kappaB pathway, which mediates NGF survival and differentiation responses.