Context-Dependent Proangiogenic Function of Bone Morphogenetic Protein Signaling Is Mediated by Disabled Homolog 2

被引：54

作者：

Kim, Jun-Dae ^{[1
]}

Kang, Hyeseon ^{[1
]}

Larrivee, Bruno ^{[1
]}

Lee, Min Young ^{[1
]}

Mettlen, Marcel ^{[2
]}

Schmid, Sandra L. ^{[2
]}

Roman, Beth L. ^{[3
]}

Qyang, Yibing ^{[1
]}

Eichmann, Anne ^{[1
]}

Jin, Suk-Won ^{[1
]}

机构：

[1] Yale Univ, Dept Internal Med, Sect Cardiovasc Med, Yale Cardiovasc Res Ctr, New Haven, CT 06511 USA

[2] Scripps Inst, Dept Cell Biol, La Jolla, CA 92037 USA

[3] Univ Pittsburg, Dept Biol Sci, Pittsburgh, PA 15260 USA

来源：

DEVELOPMENTAL CELL | 2012年 / 23卷 / 02期

基金：

美国国家卫生研究院;

关键词：

ZEBRAFISH INFORMATION NETWORK; MODEL ORGANISM DATABASE; DAB2 ADAPTER PROTEIN; ENDOTHELIAL-CELLS; BMP RECEPTORS; TGF-BETA; ANGIOGENESIS; ENDOCYTOSIS; COMPLEXES; INTERNALIZATION;

D O I：

10.1016/j.devcel.2012.07.007

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：441 / 448

页数：8

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