PUBLICATION
Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis
- Authors
- Wang, Y., Nakayama, M., Pitulescu, M.E., Schmidt, T.S., Bochenek, M.L., Sakakibara, A., Adams, S., Davy, A., Deutsch, U., Lüthi, U., Barberis, A., Benjamin, L.E., Mäkinen, T., Nobes, C.D., and Adams, R.H.
- ID
- ZDB-PUB-100511-14
- Date
- 2010
- Source
- Nature 465(7297): 483-486 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Ephrin-B2/deficiency
- Ephrin-B2/genetics
- Ephrin-B2/metabolism*
- Humans
- Lymphatic Vessels
- Mice
- Receptor, EphB4/deficiency
- Receptor, EphB4/genetics
- Receptor, EphB4/metabolism
- Lymphangiogenesis*/genetics
- Neuropeptides/metabolism
- Vascular Endothelial Growth Factor Receptor-3/metabolism
- Proto-Oncogene Proteins c-akt/metabolism
- Embryo Loss
- Endocytosis
- Extracellular Signal-Regulated MAP Kinases/metabolism
- Animals
- rac1 GTP-Binding Protein
- Endothelial Cells/cytology
- Endothelial Cells/metabolism
- Cells, Cultured
- Signal Transduction
- Female
- Vascular Endothelial Growth Factor C/metabolism*
- Embryo, Mammalian/blood supply
- Embryo, Mammalian/metabolism
- Pregnancy
- Mice, Transgenic
- Neovascularization, Physiologic*/genetics
- rac GTP-Binding Proteins/metabolism
- Zebrafish
- PubMed
- 20445537 Full text @ Nature
Citation
Wang, Y., Nakayama, M., Pitulescu, M.E., Schmidt, T.S., Bochenek, M.L., Sakakibara, A., Adams, S., Davy, A., Deutsch, U., Lüthi, U., Barberis, A., Benjamin, L.E., Mäkinen, T., Nobes, C.D., and Adams, R.H. (2010) Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis. Nature. 465(7297):483-486.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping