This Article Full Text Full Text (PDF) All Versions of this Article: 23/2/190    most recent 01.ATV.0000055440.89758.C2v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hamada, K. Articles by Suda, T. Search for Related Content PubMed PubMed Citation Articles by Hamada, K. Articles by Suda, T. Related Collections Angiogenesis Endothelium/vascular type/nitric oxide

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:190.)
© 2003 American Heart Association, Inc.

Vascular Biology

Distinct Roles of Ephrin-B2 Forward and EphB4 Reverse Signaling in Endothelial Cells

Koichi Hamada; Yuichi Oike; Yasuhiro Ito; Hiromitsu Maekawa; Keishi Miyata; Taizo Shimomura; Toshio Suda

From the Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto and Department of Cell Differentiation (Y.O., Y.I., H.M., T.S.), The Sakaguchi Laboratory, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.

Correspondence to Toshio Suda, MD, Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. E-mail sudato{at}sc.itc.keio.ac.jp

Objective— The transmembrane ligand ephrin-B2 and its receptor tyrosine kinase EphB4 are specifically expressed on arterial and venous endothelial cells, respectively, and bidirectional signals mediated by both proteins play an important role in vascular development. However, how such bidirectional signals are required for cell-cell adhesion or repulsion remains unclear.

Methods and Results— Using a cell line and sorted primary endothelial cells, we show that ephrin-B2 forward signaling through the EphB4 receptor inhibits cell adhesion, whereas EphB4 reverse signaling by the transmembrane ephrin-B2 ligand does not. Cell migration is also inhibited on immobilized ephrin-B2-Fc but not on EphB4-Fc protein.

Conclusions— Ephrin-B2 forward signaling and EphB4 reverse signaling differentially affect cell adhesion and migration between arterial and venous endothelial cells.

Key Words: ephrin-B2 • EphB4 • cell adhesion • spreading • vascular development

This article has been cited by other articles:

				D. Pfaff, M. Heroult, M. Riedel, Y. Reiss, R. Kirmse, T. Ludwig, T. Korff, M. Hecker, and H. G. Augustin Involvement of endothelial ephrin-B2 in adhesion and transmigration of EphB-receptor-expressing monocytes J. Cell Sci., November 15, 2008; 121(22): 3842 - 3850. [Abstract] [Full Text] [PDF]

				A. Zeoli, P. Dentelli, A. Rosso, G. Togliatto, A. Trombetta, L. Damiano, P. F. di Celle, L. Pegoraro, F. Altruda, and M. F. Brizzi Interleukin-3 promotes expansion of hemopoietic-derived CD45+ angiogenic cells and their arterial commitment via STAT5 activation Blood, July 15, 2008; 112(2): 350 - 361. [Abstract] [Full Text] [PDF]

				T. Korff, J. Braun, D. Pfaff, H. G. Augustin, and M. Hecker Role of ephrinB2 expression in endothelial cells during arteriogenesis: impact on smooth muscle cell migration and monocyte recruitment Blood, July 1, 2008; 112(1): 73 - 81. [Abstract] [Full Text] [PDF]

				A. Limbourg, M. Ploom, D. Elligsen, I. Sorensen, T. Ziegelhoeffer, A. Gossler, H. Drexler, and F. P. Limbourg Notch Ligand Delta-Like 1 Is Essential for Postnatal Arteriogenesis Circ. Res., February 16, 2007; 100(3): 363 - 371. [Abstract] [Full Text] [PDF]

				D. O. Zamora, M. H. Davies, S. R. Planck, J. T. Rosenbaum, and M. R. Powers Soluble Forms of EphrinB2 and EphB4 Reduce Retinal Neovascularization in a Model of Proliferative Retinopathy Invest. Ophthalmol. Vis. Sci., June 1, 2005; 46(6): 2175 - 2182. [Abstract] [Full Text] [PDF]

				G. Xia, S. R. Kumar, R. Masood, S. Zhu, R. Reddy, V. Krasnoperov, D. I. Quinn, S. M. Henshall, R. L. Sutherland, J. K. Pinski, et al. EphB4 Expression and Biological Significance in Prostate Cancer Cancer Res., June 1, 2005; 65(11): 4623 - 4632. [Abstract] [Full Text] [PDF]

				R. Masood, G. Xia, D. L. Smith, P. Scalia, J. G. Still, A. Tulpule, and P. S. Gill Ephrin B2 expression in Kaposi sarcoma is induced by human herpesvirus type 8: phenotype switch from venous to arterial endothelium Blood, February 1, 2005; 105(3): 1310 - 1318. [Abstract] [Full Text] [PDF]

				G. Serini and F. Bussolino Common Cues in Vascular and Axon Guidance Physiology, December 1, 2004; 19(6): 348 - 354. [Abstract] [Full Text] [PDF]

				N. K. Noren, M. Lu, A. L. Freeman, M. Koolpe, and E. B. Pasquale Interplay between EphB4 on tumor cells and vascular ephrin-B2 regulates tumor growth PNAS, April 13, 2004; 101(15): 5583 - 5588. [Abstract] [Full Text] [PDF]

				G. J. Hausman and R. L. Richardson Adipose tissue angiogenesis J Anim Sci, March 1, 2004; 82(3): 925 - 934. [Abstract] [Full Text] [PDF]

				Y. Oike, K. Yasunaga, Y. Ito, S.-i. Matsumoto, H. Maekawa, T. Morisada, F. Arai, N. Nakagata, M. Takeya, Y. Masuho, et al. Angiopoietin-related growth factor (AGF) promotes epidermal proliferation, remodeling, and regeneration PNAS, August 5, 2003; 100(16): 9494 - 9499. [Abstract] [Full Text] [PDF]

				T. Fuller, T. Korff, A. Kilian, G. Dandekar, and H. G. Augustin Forward EphB4 signaling in endothelial cells controls cellular repulsion and segregation from ephrinB2 positive cells J. Cell Sci., June 15, 2003; 116(12): 2461 - 2470. [Abstract] [Full Text] [PDF]