Ligand binding to LRP1 transactivates Trk receptors by a Src family kinase-dependent pathway.
Ligand binding to LRP1 transactivates Trk receptors by a Src family kinase-dependent pathway.
复制标题
DOI：
10.1126/scisignal.2000188
复制
发表时间：
2009-04-28
影响因子：
7.3
通讯作者：
Gonias SL
中科院分区：
文献类型：
--
作者：
Shi Y;Mantuano E;Inoue G;Campana WM;Gonias SL
低密度脂蛋白受体相关蛋白1（LRP 1）在多种结构不同的配体的内吞作用和细胞内信号传导中起作用。虽然LRP 1已被牵连在神经元功能的几个方面，神经元LRP 1的活性的分子机制仍然不清楚。在这里，我们描述了LRP 1反式激活Trk受体的信号通路。组织型纤溶酶原激活剂或α2-巨球蛋白（α 2 M）与LRP 1结合导致PC 12细胞和神经元中Src家族激酶（SFK）激活和SFK依赖性Trk受体反式激活。Trk受体的反式激活对于Akt和细胞外信号调节激酶的激活以及LRP 1下游的神经突生长是必要的。将α 2 M的LRP 1结合域注射到大鼠背根神经节中诱导Trk受体磷酸化，该磷酸化被受体相关蛋白阻断，受体相关蛋白是与LRP 1结合的配体的拮抗剂。Trk受体反式激活提供了一种机制，通过这种机制，不同的LRP 1配体可以表现出神经营养活性。
Low-density lipoprotein receptor-related protein 1 (LRP1) functions in endocytosis and intracellular signaling for a variety of structurally diverse ligands. Although LRP1 has been implicated in several aspects of neuronal function, molecular mechanisms underlying the activity of neuronal LRP1 remain unclear. Here, we describe a signaling pathway whereby LRP1 transactivates Trk receptors. Binding of tissue-type plasminogen activator or α2-macroglobulin (α2M) to LRP1 resulted in Src family kinase (SFK) activation and SFK-dependent Trk receptor transactivation in PC12 cells and neurons. Trk receptor transactivation was necessary for activation of Akt and extracellular signal-regulated kinase, and for neurite outgrowth downstream of LRP1. Injection of the LRP1-binding domain of α2M into rat dorsal root ganglia induced Trk receptor phosphorylation, which was blocked by receptor-associated protein, an antagonist of ligand binding to LRP1. Trk receptor transactivation provides a mechanism by which diverse LRP1 ligands may demonstrate neurotrophic activity.
登录
查看更多内容
影响因子：
20.3
作者：
Gaultier, Alban;Arandjelovic, Sanja;Gonias, Steven L.
通讯作者：
Gonias, Steven L.
DOI：
10.1083/jcb.146.1.149
发表时间：
1999-07-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Nguyen DH;Catling AD;Webb DJ;Sankovic M;Walker LA;Somlyo AV;Weber MJ;Gonias SL
通讯作者：
Gonias SL
影响因子：
4.8
作者：
Huang, W;Dolmer, K;Gettins, PGW
通讯作者：
Gettins, PGW
影响因子：
2.5
作者：
Hajebrahimi, Zahra;Mowla, Seyed Javad;Tavallaei, Mahmoud
通讯作者：
Tavallaei, Mahmoud
影响因子：
4.8
作者：
Mantuano, Elisabetta;Mukandala, Gatambwa;Gonias, Steven L.
通讯作者：
Gonias, Steven L.