EphB ligand, ephrinB2, suppresses the VEGF- and angiopoietin-1-induced Ras/mitogen-activated protein kinase pathway in venous endothelial cells

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Interaction between ephrinB2 and EphB4 in endothelial cells at the arterial-venous capillary interface is critical for proper embryonic capillary morphogenesis. However, the intracellular downstream signaling of ephrinB2-EphB in vascular endothelial cells is unknown. This study examined the effect of ephrinB2-induced activation of EphB kinases on vascular endothelial growth factor (VEGF)- and angiopoietin-1 (Ang1)-induced Ras/mitogen-activated protein kinase (MAPK) signaling cascades in human umbilical vein endothelial cells (HUVECs). Reverse transcriptase-polymer chain reaction results showed that HUVECs expressed three kinds of EphB kinases known to bind to ephrinB2: EphB2, EphB3, and EphB4. EphrinB2 not only increased the phosphorylation of EphB2 and EphB4 in a time-dependent manner but also increased recruitment of p120-Ras-GTPase-activating protein (p120-RasGAP) to EphB2 and EphB4. Accordingly, ephrinB2 inhibited VEGF- and Ang1-induced Ras-MAPK activities, whereas ephrinB2 did not alter VEGF-induced Flk phosphorylation or Ang1-induced Tie2 phosphorylation. Furthermore, ephrinB2 suppressed VEGF- and Ang1-induced proliferation and/or migration, which are mediated mainly through Ras/MAPK signaling cascades. From these results, we propose that ephrinB2-EphB, signaling through Ras/MAPK cascade, may be critical for proper morphogenesis of capillary endothelium through the arrest of endothelial cell proliferation and migration at the arterial-venous interface.
Publisher
FEDERATION AMER SOC EXP BIOL
Issue Date
2002-05
Language
English
Article Type
Article
Keywords

RECEPTOR TYROSINE KINASE; GROWTH-FACTOR; CARDIOVASCULAR DEVELOPMENT; ANGIOGENESIS; MORPHOGENESIS; PROLIFERATION; SPECIFICITY; SECRETION; SURVIVAL; TIE2

Citation

FASEB JOURNAL, v.16, no.7, pp.1126 - 1126

ISSN
0892-6638
DOI
10.1096/fj.01-0805fje
URI
http://hdl.handle.net/10203/85604
Appears in Collection
MSE-Journal Papers(저널논문)
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