Activation of Ras is necessary and sufficient for upregulation of vanilloid receptor type 1 in sensory neurons by neurotrophic factors
Activation of Ras is necessary and sufficient for upregulation of vanilloid receptor type 1 in sensory neurons by neurotrophic factors
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DOI：
10.1016/s1044-7431(02)00022-2
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发表时间：
2003-01-01
影响因子：
3.5
通讯作者：
Winter, J
中科院分区：
文献类型：
--
作者：
Bron, R;Klesse, LJ;Winter, J
我们已经分析了参与神经营养因子（NTF）诱导的伤害性的上调，特别是香草素受体1型（VR 1），由成年大鼠背根神经节神经元的信号通路。由神经生长因子和胶质细胞源性神经营养因子引起的VR 1的上调被MEK抑制剂部分阻断。显性负性Ras而非Rap阻断NTF诱导的ERK激活和VR 1上调。激活的Ras模拟NTF介导的背根神经节神经元中VR 1的诱导。磷脂酰肌醇3-激酶抑制剂LY 294002也抑制NTF诱导的VR 1上调。然而，这可能至少部分是由于NTF诱导的ERK激活的阻断。ERK和磷脂酰肌醇3-激酶的组成性同时刺激不足以使VR 1上调。总之，这些数据表明，VR 1的背根神经节神经元的表达是由常见的Ras依赖性途径。(C)2003 Elsevier Science（美国）。All rights reserved.
We have analyzed signaling pathways involved in neurotrophic factor (NTF)-induced upregulation of nociceptive properties, specifically vanilloid receptor type 1 (VR1), by adult rat dorsal root ganglion neurons. Upregulation of VR1 by nerve growth factor and glial cell line-derived neurotrophic factor is partially blocked by a MEK inhibitor. Dominant negative Ras, but not Rap, blocks NTF-induced ERK activation and VR1 upregulation, Activated Ras mimics NTF-mediated induction of VR1 in dorsal root ganglion neurons. An inhibitor of phosphatidylinositol 3-kinase, LY294002, also inhibited NTF-induced VR1 upregulation. However, this may at least in part be due to a block of NTF-induced ERK activation. Constitutive simultaneous stimulation of both ERK and phosphatidylinositol 3-kinase is not sufficient for VR1 upregulation. Together, the data suggest that VR1 expression by dorsal root ganglion neurons is regulated by common Ras-dependent pathways. (C) 2003 Elsevier Science (USA). All rights reserved.