Ephrin-B2 regulates endothelial cell morphology and motility independently of Eph-receptor binding
Open Access
- 15 April 2010
- journal article
- research article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 123 (8), 1235-1246
- https://doi.org/10.1242/jcs.061903
Abstract
The transmembrane protein ephrin-B2 regulates angiogenesis, i.e. the formation of new blood vessels through endothelial sprouting, proliferation and remodeling processes. In addition to essential roles in the embryonic vasculature, ephrin-B2 expression is upregulated in the adult at sites of neovascularization, such as tumors and wounds. Ephrins are known to bind Eph receptor family tyrosine kinases on neighboring cells and trigger bidirectional signal transduction downstream of both interacting molecules. Here we show that ephrin-B2 dynamically modulates the motility and cellular morphology of isolated endothelial cells. Even in the absence of Eph-receptor binding, ephrin-B2 stimulates repeated cycling between actomyosin-dependent cell contraction and spreading episodes, which requires the presence of the C-terminal PDZ motif. Our results show that ephrin-B2 is a potent regulator of endothelial cell behavior, and indicate that the control of cell migration and angiogenesis by ephrins might involve both receptor-dependent and receptor-independent activities.Keywords
This publication has 57 references indexed in Scilit:
- The phosphorylation of ephrin‐B2 ligand promotes glioma cell migration and invasionInternational Journal of Cancer, 2009
- Ephrin-independent regulation of cell substrate adhesion by the EphB4 receptorBiochemical Journal, 2009
- EphrinB reverse signaling contributes to endothelial and mural cell assembly into vascular structuresBlood, 2009
- Coordination of Rho GTPase activities during cell protrusionNature, 2009
- Ephrin-B1 regulates axon guidance by reverse signaling through a PDZ-dependent mechanismGenes & Development, 2009
- Paradoxes of the EphB4 Receptor in CancerCancer Research, 2007
- Co-operative Cdc42 and Rho signalling mediates ephrinB-triggered endothelial cell retractionBiochemical Journal, 2007
- Eph receptor signalling casts a wide net on cell behaviourNature Reviews Molecular Cell Biology, 2005
- Retinal Axon Response to Ephrin-As Shows a Graded, Concentration-Dependent Transition from Growth Promotion to InhibitionNeuron, 2004
- Crystal structure of an Eph receptor–ephrin complexNature, 2001