Context-dependent proangiogenic function of bone morphogenetic protein signaling is mediated by disabled homolog 2.
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.
Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, CT 06511, USA.
Jun-Dae
JD
Kim
Hyeseon
H
Kang
Bruno
B
Larrivée
Min Young
MY
Lee
Marcel
M
Mettlen
Sandra L
SL
Schmid
Beth L
BL
Roman
Yibing
Y
Qyang
Anne
A
Eichmann
Suk-Won
SW
Jin
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000098:blood supply / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D018919:Neovascularization, Physiologic; D010766:Phosphorylation; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D051017:Apoptosis Regulatory Proteins; D019485:Bone Morphogenetic Proteins; C102885:DAB2 protein, human; C543404:Dab2 protein, zebrafish; D025521:Tumor Suppressor Proteins; D029961:Zebrafish Proteins