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

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

Research output: Contribution to journalArticle

42 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)441-448
Number of pages8
JournalDevelopmental Cell
Volume23
Issue number2
DOIs
StatePublished - Aug 14 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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    Kim, J. D., Kang, H., Larrivée, B., Lee, M. Y., Mettlen, M., Schmid, S. L., Roman, B. L., Qyang, Y., Eichmann, A., & Jin, S. W. (2012). Context-Dependent Proangiogenic Function of Bone Morphogenetic Protein Signaling Is Mediated by Disabled Homolog 2. Developmental Cell, 23(2), 441-448. https://doi.org/10.1016/j.devcel.2012.07.007