EphB receptors and ephrinB ligands: regulators of vascular assembly and homeostasis
Eph receptors comprise the largest family of receptor tyrosine kinases consisting of eight EphA receptors (with five corresponding glycosyl-phosphatidyl-inositol-anchored ephrinA ligands) and six EphB receptors (with three corresponding transmembrane ephrinB ligands). Originally identified as neuronal pathfinding molecules, genetic loss of function experiments have identified EphB receptors and ephrinB ligands as crucial regulators of vascular assembly, orchestrating arteriovenous differentiation and boundary formation. Despite these clearly defined rate-limiting roles of the EphB/ephrinB system for developmental angiogenesis, the mechanisms of the functions of EphB receptors and ephrinB ligands in the cells of the vascular system are poorly understood. Moreover, little evidence can be found in the recent literature regarding complementary EphB and ephrinB expression patterns that occur in the vascular system and that may bring cells into juxtapositional contact to allow bi-directional signaling between neighboring cells. This review summarizes the current knowledge of the role of EphB receptors and ephrinB ligands during embryonic vascular assembly and discusses recent findings on EphB/ephrinB-mediated cellular functions pointing to the crucial role of the Eph/ephrin system in controlling vascular homeostasis in the adult.
KeywordsEndothelial cells Angiogenesis Eph Ephrin Homeostasis
- Chen E, Xia G, Kundra A, Smith DL, Masood R, Gill P (2003) EphB4/ephrinB2 expression by malignant mesothelioma as a potential therapeutic target. Proc Am Assoc Cancer Res 44:475Google Scholar
- Oike Y, Ito Y, Hamada K, Zhang XQ, Miyata K, Arai F, Inada T, Araki K, Nakagata N, Takeya M, Kisanuki YY, Yanagisawa M, Gale NW, Suda T (2002) Regulation of vasculogenesis and angiogenesis by EphB/ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells. Blood 100:1326–1333PubMedGoogle Scholar
- Palmer A, Klein R (2003) Multiple roles of ephrins in morphogenesis, neuronal networking, and brain function. Genes Dev 17:(in press)Google Scholar
- Pandey A, Shao H, Marks RM, Polverini PJ, Dixit VM (1995) Role of B61, the ligand for the Eck receptor tyrosine kinase, in TNF-alpha-induced angiogenesis. Science 268:567–569Google Scholar
- Shin D, Garcia-Cardena G, Hayashi SI, Gerety S, Asahara T, Stavrakis G, Isner J, Folkman J, Gimbrone MA, Anderson DJ (2001) Expression of ephrinB2 identifies a stable genetic difference between arterial and venous vascular smooth muscle as well as endothelial cells, and marks subsets of microvessels at sites of adult neovascularization. Dev Biol 230:139–150PubMedGoogle Scholar