ACTIVATION OF THE SPHINGOMYELIN CYCLE THROUGH THE LOW-AFFINITY NEUROTROPHIN RECEPTOR
ACTIVATION OF THE SPHINGOMYELIN CYCLE THROUGH THE LOW-AFFINITY NEUROTROPHIN RECEPTOR
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DOI：
10.1126/science.8079174
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发表时间：
1994-09-09
期刊：
影响因子：
56.9
通讯作者：
HANNUN, YA
中科院分区：
文献类型：
--
作者：
DOBROWSKY, RT;WERNER, MH;HANNUN, YA
低亲和力神经营养因子受体（p75（NTR））在信号转导中的作用尚不明确。神经生长因子可以激活鞘磷脂循环，产生假定的脂质第二信使神经酰胺。在T9神经胶质瘤细胞中，加入细胞可渗透的神经酰胺类似物模拟神经生长因子对细胞生长抑制和突起形成的影响。在T9细胞和过表达p75（NTR）的NIH 3 T3细胞中，该信号通路似乎由p75（NTR）介导。表皮生长因子受体-p75（NTR）嵌合体在T9细胞中的表达赋予表皮生长因子激活鞘磷脂循环的能力。这些数据表明，p75（NTR）能够独立于trk神经营养因子受体（p140（trk））的信号传导，神经酰胺可能是神经营养因子生物学中的介质。
The role of the low-affinity neurotrophin receptor (p75(NTR)) in signal transduction is undefined. Nerve growth factor can activate the sphingomyelin cycle, generating the putative-lipid second messenger ceramide. In T9 glioma cells, addition of a cell-permeable ceramide analog mimicked the effects of nerve growth factor on cell growth inhibition and process formation. This signaling pathway appears to be mediated by p75(NTR) in T9 cells and NIH 3T3 cells overexpressing p75(NTR). Expression of an epidermal growth factor receptor-p75(NTR) chimera in T9 cells imparted to epidermal growth factor the ability to activate the sphingomyelin cycle. These data demonstrate that p75(NTR) is capable of signaling independently of the trk neurotrophin receptor (p140(trk)) and that ceramide may be a mediator in neurotrophin biology.