HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 9, 5702-5710, March 3, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/9/5702    most recent M511941200v1 Submit a Letter to Editor 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 von Wronski, M. A. Articles by Nunn, A. D. Search for Related Content PubMed PubMed Citation Articles by von Wronski, M. A. Articles by Nunn, A. D. Social Bookmarking                      What's this?

Tuftsin Binds Neuropilin-1 through a Sequence Similar to That Encoded by Exon 8 of Vascular Endothelial Growth Factor^*

Mathew A. von Wronski¹, Natarajan Raju, Radhakrishna Pillai, Nancy J. Bogdan, Edmund R. Marinelli, Palaniappa Nanjappan, Kondareddiar Ramalingam, Thangavel Arunachalam, Steve Eaton, Karen E. Linder, Feng Yan, Sibylle Pochon, Michael F. Tweedle, and Adrian D. Nunn

From the Ernst Felder Laboratories, Bracco Research USA, Princeton, New Jersey 08540 and Bracco Research S.A., 31 Rt. De la Galaise, CH-1228 Plan-les-Ouates, Geneva, Switzerland

Tuftsin, Thr-Lys-Pro-Arg (TKPR), is an immunostimulatory peptide with reported nervous system effects as well. We unexpectedly found that tuftsin and a higher affinity antagonist, TKPPR, bind selectively to neuropilin-1 and block vascular endothelial growth factor (VEGF) binding to that receptor. Dimeric and tetrameric forms of TKPPR had greatly increased affinity for neuropilin-1 based on competition binding experiments. On endothelial cells tetrameric TKPPR inhibited the VEGF₁₆₅-induced autophosphorylation of vascular endothelial growth factor receptor-2 (VEGFR-2) even though it did not directly inhibit VEGF binding to VEGFR-2. Homology between exon 8 of VEGF and TKPPR suggests that the sequence coded for by exon 8 may stabilize VEGF binding to neuropilin-1 to facilitate signaling through VEGFR-2. Given the overlap between processes involving neuropilin-1 and tuftsin, we propose that at least some of the previously reported effects of tuftsin are mediated through neuropilin-1.

Received for publication, November 4, 2005

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Bracco Research USA, 305 College Rd.East, Princeton, NJ 08540. Tel.: 609-514-2436; Fax: 609-514-2446; E-mail: mvonwron{at}bru.bracco.com.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Lambert, M. Bouttier, R. Vassy, M. Seigneuret, C. Petrow-Sadowski, S. Janvier, N. Heveker, F. W. Ruscetti, G. Perret, K. S. Jones, et al. HTLV-1 uses HSPG and neuropilin-1 for entry by molecular mimicry of VEGF165 Blood, May 21, 2009; 113(21): 5176 - 5185. [Abstract] [Full Text] [PDF]

				K. S. Jones, Y. K. Huang, S. A. Chevalier, P. V. Afonso, C. Petrow-Sadowski, D. C. Bertolette, A. Gessain, F. W. Ruscetti, and R. Mahieux The Receptor Complex Associated with Human T-Cell Lymphotropic Virus Type 3 (HTLV-3) Env-Mediated Binding and Entry Is Distinct from, but Overlaps with, the Receptor Complexes of HTLV-1 and HTLV-2 J. Virol., May 15, 2009; 83(10): 5244 - 5255. [Abstract] [Full Text] [PDF]

				S. Cebe-Suarez, F. S. Grunewald, R. Jaussi, X. Li, L. Claesson-Welsh, D. Spillmann, A. A. Mercer, A. E. Prota, and K. Ballmer-Hofer Orf virus VEGF-E NZ2 promotes paracellular NRP-1/VEGFR-2 coreceptor assembly via the peptide RPPR FASEB J, August 1, 2008; 22(8): 3078 - 3086. [Abstract] [Full Text] [PDF]

				I. Vetter, W. Cheng, M. Peiris, B. D. Wyse, S. J. Roberts-Thomson, J. Zheng, G. R. Monteith, and P. J. Cabot Rapid, Opioid-sensitive Mechanisms Involved in Transient Receptor Potential Vanilloid 1 Sensitization J. Biol. Chem., July 11, 2008; 283(28): 19540 - 19550. [Abstract] [Full Text] [PDF]

				Y. Glinka and G. J. Prud'homme Neuropilin-1 is a receptor for transforming growth factor {beta}-1, activates its latent form, and promotes regulatory T cell activity J. Leukoc. Biol., July 1, 2008; 84(1): 302 - 310. [Abstract] [Full Text] [PDF]

				E. Sulpice, J. Plouet, M. Berge, D. Allanic, G. Tobelem, and T. Merkulova-Rainon Neuropilin-1 and neuropilin-2 act as coreceptors, potentiating proangiogenic activity Blood, February 15, 2008; 111(4): 2036 - 2045. [Abstract] [Full Text] [PDF]

				P. Mineur, A. C. Colige, Christophe. F. Deroanne, J. Dubail, F. Kesteloot, Y. Habraken, A. Noel, S. Voo, J. Waltenberger, C. M. Lapiere, et al. Newly identified biologically active and proteolysis-resistant VEGF-A isoform VEGF111 is induced by genotoxic agents J. Cell Biol., December 17, 2007; 179(6): 1261 - 1273. [Abstract] [Full Text] [PDF]

				D. Krilleke, A. DeErkenez, W. Schubert, I. Giri, G. S. Robinson, Y.-S. Ng, and D. T. Shima Molecular Mapping and Functional Characterization of the VEGF164 Heparin-binding Domain J. Biol. Chem., September 21, 2007; 282(38): 28045 - 28056. [Abstract] [Full Text] [PDF]

				Q. Pan, Y. Chathery, Y. Wu, N. Rathore, R. K. Tong, F. Peale, A. Bagri, M. Tessier-Lavigne, A. W. Koch, and R. J. Watts Neuropilin-1 Binds to VEGF121 and Regulates Endothelial Cell Migration and Sprouting J. Biol. Chem., August 17, 2007; 282(33): 24049 - 24056. [Abstract] [Full Text] [PDF]

				M. A. von Wronski, M. F. Tweedle, and A. D. Nunn Binding of the C-terminal amino acids of VEGF121 directly with neuropilin-1 should be considered FASEB J, May 1, 2007; 21(7): 1292 - 1292. [Full Text] [PDF]

				C. W. Vander Kooi, M. A. Jusino, B. Perman, D. B. Neau, H. D. Bellamy, and D. J. Leahy Structural basis for ligand and heparin binding to neuropilin B domains PNAS, April 10, 2007; 104(15): 6152 - 6157. [Abstract] [Full Text] [PDF]

				M. K. Inder, N. Ueda, A. A. Mercer, S. B. Fleming, and L. M. Wise Bovine papular stomatitis virus encodes a functionally distinct VEGF that binds both VEGFR-1 and VEGFR-2 J. Gen. Virol., March 1, 2007; 88(3): 781 - 791. [Abstract] [Full Text] [PDF]

				H. Jia, A. Bagherzadeh, B. Hartzoulakis, A. Jarvis, M. Lohr, S. Shaikh, R. Aqil, L. Cheng, M. Tickner, D. Esposito, et al. Characterization of a Bicyclic Peptide Neuropilin-1 (NP-1) Antagonist (EG3287) Reveals Importance of Vascular Endothelial Growth Factor Exon 8 for NP-1 Binding and Role of NP-1 in KDR Signaling J. Biol. Chem., May 12, 2006; 281(19): 13493 - 13502. [Abstract] [Full Text] [PDF]