Morphogenesis of human endothelial cells is inhibited by DAB2 via Src

Abstract 

Disabled-2 (DAB2) is an adaptor protein implicated in signal transduction pathways and in protein traffic regulation. Here, we show that DAB2 is highly expressed in human endothelial cells. DAB2 silencing in endothelial cells by lentiviral-mediated small hairpin RNA expression affects cell migration and differentiation into capillary-like structures while increasing cell proliferation and viability. DAB2 knockdown causes activation of the Src-FAK signal pathway, extracellular-signal regulated kinase and c-Jun NH₂-terminal kinase activation, and inhibition of p38 phosphorylation. In DAB2 silenced endothelial cells, pharmacological inhibition of Src with its specific inhibitor PP2 abolishes focal adhesion kinase activation and restores differentiation of endothelial cells. These results suggest that DAB2, via Src and focal adhesion signaling, plays a role in human endothelial cell function.

Abbreviations: DAB2, Disabled-2, HUVEC, human umbilical vein endothelial cells, MAPK, mitogen-activated protein kinase, ERK, extracellular-signal regulated kinase, FAK, focal adhesion kinase, JNK, c-Jun NH₂-terminal kinase

Keywords: Angiogenesis, Disabled-2, RNA interference, Focal adhesion kinase, Src, Mitogen-activated protein kinase