Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis

Wang, Yingdi; Nakayama, Masanori; Pitulescu, Mara E; Schmidt, Tim S; Bochenek, Magdalena L; Sakakibara, Akira; Adams, Susanne; Davy, Alice; Deutsch, Urban; Lüthi, Urs; Barberis, Alcide; Benjamin, Laura E; Mäkinen, Taija; Nobes, Catherine D; Adams, Ralf H (2010). Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis. Nature, 465(7297), pp. 483-6. London: Macmillan Journals Ltd. 10.1038/nature09002

Full text not available from this repository.

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. Although it is already appreciated that angiogenesis is triggered by tissue-derived signals, such as vascular endothelial growth factor (VEGF) family growth factors, the resulting signalling processes in endothelial cells are only partly understood. Here we show with genetic experiments in mouse and zebrafish that ephrin-B2, a transmembrane ligand for Eph receptor tyrosine kinases, promotes sprouting behaviour and motility in the angiogenic endothelium. We link this pro-angiogenic 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 internalization of VEGFR3 in cultured cells and mutant mice is defective, which compromises downstream signal transduction by the small GTPase Rac1, Akt and the mitogen-activated protein kinase Erk. Our results show that full VEGFR3 signalling is coupled to receptor internalization. Ephrin-B2 is a key regulator of this process and thereby controls angiogenic and lymphangiogenic growth.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute
UniBE Contributor:	Deutsch, Urban
ISSN:	0028-0836
Publisher:	Macmillan Journals Ltd.
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:11
Last Modified:	05 Dec 2022 14:01
Publisher DOI:	10.1038/nature09002
PubMed ID:	20445537
Web of Science ID:	000278043700036
URI:	https://boris.unibe.ch/id/eprint/2157 (FactScience: 204413)