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Prepublished online as a Blood First Edition Paper on May 22, 2003; DOI 10.1182/blood-2002-12-3634. This Article Full Text (PDF) All Versions of this Article: 2002-12-3634v1 102/6/2099    most recent Alert me when this article is cited Alert me if a correction is posted 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Licht, T. Articles by Ben-Sasson, S. A Search for Related Content PubMed PubMed Citation Articles by Licht, T. Articles by Ben-Sasson, S. A Social Bookmarking                   What's this? Submitted December 3, 2002 Accepted May 10, 2003 Induction of pro-angiogenic signaling by a synthetic peptide derived from the 2nd intracellular loop of S1P3(EDG3) Tamar Licht, Lilia Tsirulnikov, Hadas Reuveni, Talia Yarnitzky, and Shmuel A Ben-Sasson* Keryx Biopharmaceuticals, Jerusalem, Israel Department of Experimental Medicine and Cancer Research, The Hebrew University - Hadassah Medical School, Jerusalem, Israel * Corresponding author; email: muli{at}md.huji.ac.il. The G-protein coupled receptors of the endothelial differentiation gene (EDG) family mediate pro-angiogenic activities, such as endothelial cell proliferation, chemotaxis, and vessel morphogenesis. We synthesized and tested the effects of a nine-amino acid peptide (KRX-725), derived from the second intracellular loop of S1P3 (EDG3). KRX-725 mimics the effects of sphingosine 1-phosphate (S1P), the natural ligand of S1P3, by triggering a Gi-dependent MEK-ERK signal transduction pathway. Utilizing aortic rings as an ex-vivo model of angiogenesis, vascular sprouting was assessed in the presence of KRX-725 or S1P. KRX-725 induced extensive and dense vascular sprouts, which contain an elaborated organization of endothelial and smooth muscle layers, including lumen formation. When KRX-725 or S1P were combined with pro-angiogenic factors like basic fibroblast growth factor (bFGF), stem cell factor or vascular endothelial growth factor, the effect was synergistic, leading to further enhancement of vascular sprouting. KRX-725 also initiated neovascularization in a mouse corneal pocket assay in vivo and showed synergism with bFGF. The specificity of KRX-725 was demonstrated via peptide-induced receptor internalization of S1P3 but not S1P1. The ability of a short peptide to stimulate extensive angiogenesis and to synergize with pro-angiogenic factors, suggest that KRX-725 may serve as a useful agent in treating pathologic conditions such as peripheral vascular disease, cardiac ischemia or tissue grafts. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Song, Y. Huang, H. Shi, S. Yuan, Y. Ding, X. Song, Y. Fu, and Y. Luo Overexpression of Platelet-Derived Growth Factor-BB Increases Tumor Pericyte Content via Stromal-Derived Factor-1{alpha}/CXCR4 Axis Cancer Res., August 1, 2009; 69(15): 6057 - 6064. [Abstract] [Full Text] [PDF] C. K. Means and J. H. Brown Sphingosine-1-phosphate receptor signalling in the heart Cardiovasc Res, May 1, 2009; 82(2): 193 - 200. [Abstract] [Full Text] [PDF] S. Sakao, L. Taraseviciene-Stewart, C. D. Cool, Y. Tada, Y. Kasahara, K. Kurosu, N. Tanabe, Y. Takiguchi, K. Tatsumi, T. Kuriyama, et al. VEGF-R blockade causes endothelial cell apoptosis, expansion of surviving CD34+ precursor cells and transdifferentiation to smooth muscle-like and neuronal-like cells FASEB J, November 1, 2007; 21(13): 3640 - 3652. [Abstract] [Full Text] [PDF] S. Bonnaud, C. Niaudet, G. Pottier, M.-H. Gaugler, J. Millour, J. Barbet, L. Sabatier, and F. Paris Sphingosine-1-Phosphate Protects Proliferating Endothelial Cells from Ceramide-Induced Apoptosis but not from DNA Damage-Induced Mitotic Death Cancer Res., February 15, 2007; 67(4): 1803 - 1811. [Abstract] [Full Text] [PDF] D. H. Walter, U. Rochwalsky, J. Reinhold, F. Seeger, A. Aicher, C. Urbich, I. Spyridopoulos, J. Chun, V. Brinkmann, P. Keul, et al. Sphingosine-1-Phosphate Stimulates the Functional Capacity of Progenitor Cells by Activation of the CXCR4-Dependent Signaling Pathway via the S1P3 Receptor Arterioscler Thromb Vasc Biol, February 1, 2007; 27(2): 275 - 282. [Abstract] [Full Text] [PDF] O. Kaidanovich-Beilin and H. Eldar-Finkelman Peptides Targeting Protein Kinases: Strategies and Implications. Physiology, December 1, 2006; 21(6): 411 - 418. [Abstract] [Full Text] [PDF] M. Y. Niv, H. Rubin, J. Cohen, L. Tsirulnikov, T. Licht, A. Peretzman-Shemer, E. Cna'an, A. Tartakovsky, I. Stein, S. Albeck, et al. Sequence-based Design of Kinase Inhibitors Applicable for Therapeutics and Target Identification J. Biol. Chem., January 9, 2004; 279(2): 1242 - 1255. [Abstract] [Full Text] [PDF]

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