Ephrin-B2 regulates endothelial cell morphology and motility independently of Eph-receptor binding.
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.
Department of Physiology and Pharmacology, University of Bristol, Bristol BS8 1TD, UK.
Magdalena L
ML
Bochenek
Sarah
S
Dickinson
Jonathan W
JW
Astin
Ralf H
RH
Adams
Catherine D
CD
Nobes
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D020816:Amino Acid Motifs; D002465:Cell Movement; D048430:Cell Shape; D022081:Cell Surface Extensions / Q000378:metabolism; D004705:Endocytosis; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D036388:Ephrin-B2 / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D015513:Oncogene Proteins / Q000378:metabolism; D009928:Organ Specificity; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D036082:Receptor, EphA1 / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology; D020744:rac GTP-Binding Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D036388:Ephrin-B2; C485544:NCK2 protein, human; D015513:Oncogene Proteins; D036082:Receptor, EphA1; D020744:rac GTP-Binding Proteins