Morphogenesis of human endothelial cells is inhibited by DAB2 via Src.
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.
Orlandini
Maurizio
M
Dipartimento di Biologia Molecolare, Università degli Studi di Siena, via Fiorentina, Siena, Italy.
Nucciotti
Sara
S
Galvagni
Federico
F
Bardelli
Monia
M
Rocchigiani
Marina
M
Petraglia
Felice
F
Oliviero
Salvatore
S
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000254:growth & development* / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009024:Morphogenesis; D018919:Neovascularization, Physiologic / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D025521:Tumor Suppressor Proteins; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C102885:DAB2 protein, human; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases; D020929:Mitogen-Activated Protein Kinase Kinases