Activin receptor-like kinase (ALK)1 is an antagonistic mediator of lateral TGFP/ALK5 signaling
Activin receptor-like kinase (ALK)1 is an antagonistic mediator of lateral TGFP/ALK5 signaling
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DOI：
10.1016/s1097-2765(03)00386-1
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发表时间：
2003-10-01
期刊：
影响因子：
16
通讯作者：
ten Dijke, P
中科院分区：
文献类型：
--
作者：
Goumans, MJ;Valdimarsdottir, G;ten Dijke, P
转化生长因子-β（TGF β）通过两个相反的I型受体/Smad途径调节内皮的活化状态。激活素受体样激酶-1（ALK 1）诱导Smad 1/5磷酸化，导致内皮细胞增殖和迁移增加，而ALK 5促进Smad 2/3激活并抑制这两个过程。在这里，我们报告说，ALK 5是重要的TGF β/ALK 1信号;内皮细胞缺乏ALK 5是缺乏TGF β/ALK 1诱导的反应。更具体地说，我们表明ALK 5介导ALK 1依赖于TGF β的募集进入TGF β受体复合物，并且ALK 5激酶活性是最佳ALK 1激活所需的。TGF β II型受体也是TGF β激活ALK 1所必需的。有趣的是，ALK 1不仅诱导与ALK 5相反的生物学反应，而且还直接拮抗ALK 5/Smad信号传导。
Transforming growth factor-beta (TGFbeta) regulates the activation state of the endothelium via two opposing type I receptor/Smad pathways. Activin receptor-like kinase-1 (ALK1) induces Smad1/5 phosphorylation, leading to an increase in endothelial cell proliferation and migration, while ALK5 promotes Smad2/3 activation and inhibits both processes. Here, we report that ALK5 is important for TGFbeta/ALK1 signaling; endothelial cells lacking ALK5 are deficient in TGFbeta/ALK1-induced responses. More specifically, we show that ALK5 mediates a TGFbeta-dependent recruitment of ALK1 into a TGFbeta receptor complex and that the ALK5 kinase activity is required for optimal ALK1 activation. TGFbeta type II receptor is also required for ALK1 activation by TGFbeta. Interestingly, ALK1 not only induces a biological response opposite to that of ALK5 but also directly antagonizes ALK5/Smad signaling.