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

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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:

04 May 2014 23:05

Publisher DOI:

10.1038/nature09002

PubMed ID:

20445537

Web of Science ID:

000278043700036

URI:

https://boris.unibe.ch/id/eprint/2157 (FactScience: 204413)

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