ZFIN ID: ZDB-PUB-120822-7
Context-dependent proangiogenic function of bone morphogenetic protein signaling is mediated by disabled homolog 2
Kim, J.D., Kang, H., Larrivée, B., Lee, M.Y., Mettlen, M., Schmid, S.L., Roman, B.L., Qyang, Y., Eichmann, A., and Jin, S.W.
Date: 2012
Source: Developmental Cell   23(2): 441-448 (Journal)
Registered Authors: Jin, Suk-Won, Kang, Hyeseon, Kim, Jun-Dae, Roman, Beth
Keywords: none
MeSH Terms:
  • Adaptor Proteins, Signal Transducing/genetics
  • Adaptor Proteins, Signal Transducing/metabolism*
  • Adaptor Proteins, Vesicular Transport/genetics
  • Adaptor Proteins, Vesicular Transport/metabolism*
  • Animals
  • Bone Morphogenetic Proteins/metabolism
  • Embryo, Nonmammalian/blood supply
  • Embryo, Nonmammalian/metabolism
  • Endothelial Cells/metabolism
  • Humans
  • Neovascularization, Physiologic*
  • Phosphorylation
  • Signal Transduction*
  • Tumor Suppressor Proteins
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 22898784 Full text @ Dev. Cell

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.