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

Authors: Kim, Jun-Dae; Kang, Hyeseon; Larrivée, Bruno; Lee, Min Young; Mettlen, Marcel; Schmid, Sandra L.; Roman, Beth L.; +3 Authors

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

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.

Keywords

Embryo, Nonmammalian, Tumor Suppressor Proteins, Endothelial Cells, Neovascularization, Physiologic, Zebrafish Proteins, Adaptor Proteins, Vesicular Transport, Bone Morphogenetic Proteins, Animals, Humans, Phosphorylation, Apoptosis Regulatory Proteins, Zebrafish, Developmental Biology, Adaptor Proteins, Signal Transducing, Signal Transduction

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    61
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
61
Top 10%
Top 10%
Top 10%
hybrid