Context-dependent proangiogenic function of bone morphogenetic protein signaling is mediated by disabled homolog 2

骨形态发生蛋白信号的上下文依赖性促血管生成功能由禁用的同源物 2 介导

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作者:Jun-Dae Kim, Hyeseon Kang, Bruno Larrivée, Min Young Lee, Marcel Mettlen, Sandra L Schmid, Beth L Roman, Yibing Qyang, Anne Eichmann, Suk-Won Jin

Abstract

Bone morphogenetic proteins (BMPs) have diverse functions during development in vertebrates. We have recently shown that BMP2 signaling promotes venous-specific angiogenesis in zebrafish embryos. However, factors that confer a context-dependent proangiogenic function of BMP2 signaling within endothelial cells need to be identified. Here, we report that Disabled homolog 2 (Dab2), a cargo-specific adaptor protein for Clathrin, is essential to mediate the proangiogenic function of BMP2 signaling. We find that inhibition of Dab2 attenuates internalization of BMP receptors and abrogates the proangiogenic effects of BMP signaling in endothelial cells. Moreover, inhibition of Dab2 decreases phosphorylation of SMAD-1, 5, and 8, indicating that Dab2 plays an essential role in determining the outcome of BMP signaling within endothelial cells and may provide a molecular basis for a context-dependent proangiogenic function of BMP2 signaling.

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