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Category CDBセミナー
Date and Time 2010-01-13 16:30 - 17:30
Venue Seminar Room A7F
Speaker Masanori Nakayama
Affiliation Max-Planck-Institute for Molecular Biomedicine, Department of tissue morphogenesis
Title Regulation of VEGF-induced angiogenesis by receptor endocytosis
Poster click here to download(PDF)
Host Shinichi Nishikawa
Summary In development, tissue regeneration or certain diseases, angiogenic growth leads to the expansion of blood vessels and the lymphatic
vasculature. This involves endothelial cell proliferation as well as angiogenic sprouting, in which a subset of cells, termed tip cells,
acquires motile, invasive behaviour and extends filopodial protrusions. While it is already appreciated that angiogenesis is
triggered by tissue-derived signals, such as VEGF family growth factors, the resulting signaling processes in endothelial cells are
only partially understood.

We show that ephrin-B2, a transmembrane ligand for Eph receptor tyrosine kinases, promotes sprouting behaviour and motility in the
angiogenic endothelium. We attribute this function to a crucial role of ephrin-B2 in the VEGF signalling pathway, which we have studied in
detail for VEGFR3, the receptor for VEGF-C. In the absence of ephrin-B2, the internalisation of VEGFR3 in cultured cells and mutant mice is
defective, which compromises downstream signal transduction. Our results show that full VEGFR3 signalling requires receptor
internalisation. Ephrin-B2 is a key regulator of this step and thereby controls angiogenic and lymphangiogenic growth.
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