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首页> 外文期刊>Journal of cellular biochemistry. >Characterization of epidermal growth factor receptor function in lysophosphatidic acid signaling in PC12 cells.
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Characterization of epidermal growth factor receptor function in lysophosphatidic acid signaling in PC12 cells.

机译:表皮生长因子受体在PC12细胞中的溶血磷脂酸信号中的功能表征。

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摘要

Lysophosphatidic acid (LPA) is a lipid metabolite that induces the activation of mitogen-activated protein kinase (MAPK) through binding to the G protein-coupled receptor in a number of cell lines and cultures. Recent studies have revealed that LPA is able to rapidly induce the phosphorylation of MAPK through an epidermal growth factor (EGF) receptor-dependent pathway. We investigated the role of the EGF receptor in the signaling pathway initiated by LPA stimulation in nerve growth factor (NGF)-responsive PC12 cells well known to transiently retract their own neurites upon LPA stimulation. LPA-stimulated MAPK signaling was suppressed by the selective EGF receptor inhibitor and in the dominant negative mutant EGF receptor cell line. As in the EGF signaling pathway, the complex of EGF receptor with adapter proteins Shc and Sos was formed in response to LPA stimulation, suggesting there is an intracellular mechanism for transactivation. A neurite retraction assay was also performed to examine the role of the EGF receptor in PC12 cell differentiation, which related to the involvement of LPA-induced neurite retraction. These results suggest that the receptor tyrosine kinase can be activated in a ligand-independent manner through intracellular crosstalk between the signaling pathways. Copyright 2000 Wiley-Liss, Inc.
机译:溶血磷脂酸(LPA)是一种脂质代谢产物,通过与许多细胞系和培养物中的G蛋白偶联受体结合,诱导丝裂原激活的蛋白激酶(MAPK)活化。最近的研究表明,LPA能够通过表皮生长因子(EGF)受体依赖性途径快速诱导MAPK磷酸化。我们研究了EGF受体在LPA刺激引发的神经生长因子(NGF)反应性PC12细胞中由LPA刺激引发的信号通路中的作用,众所周知,该PC12细胞在LPA刺激后会暂时撤回其神经突。 LPA刺激的MAPK信号被选择性EGF受体抑制剂和显性负突变EGF受体细胞系抑制。就像在EGF信号通路中一样,EGF受体与衔接蛋白Shc和Sos的复合物是在LPA刺激下形成的,这表明存在细胞内激活机制。还进行了神经突退缩试验,以检查EGF受体在PC12细胞分化中的作用,这与LPA诱导的神经突缩回的参与有关。这些结果表明,受体酪氨酸激酶可以通过信号通路之间的细胞内串扰以配体非依赖性的方式被激活。版权所有2000 Wiley-Liss,Inc.

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