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Morphogenesis of human endothelial cells is inhibited by DAB2 via Src
Author(s) -
Orlandini Maurizio,
Nucciotti Sara,
Galvagni Federico,
Bardelli Monia,
Rocchigiani Marina,
Petraglia Felice,
Oliviero Salvatore
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.06.025
Subject(s) - microbiology and biotechnology , proto oncogene tyrosine protein kinase src , focal adhesion , signal transduction , biology , endothelial stem cell , chemistry , biochemistry , in vitro
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 NH 2 ‐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.