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

This Article Full Text Full Text (PDF) Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wierzbicka-Patynowski, I. Articles by McLane, M. A. Search for Related Content PubMed PubMed Citation Articles by Wierzbicka-Patynowski, I. Articles by McLane, M. A.

J Biol Chem, Vol. 274, Issue 53, 37809-37814, December 31, 1999

Structural Requirements of Echistatin for the Recognition of _v3 and ₅₁ Integrins^*

Iwona Wierzbicka-Patynowski^§¶, Stefan Niewiarowski^§, Cezary Marcinkiewicz^§, Juan J. Calvete^**, Mariola M. Marcinkiewicz^§, and Mary Ann McLane^¶

From the  Physiology Department, Temple University and ^§ Sol Sherry Thrombosis Research Center, Philadelphia, Pennsylvania 19140, the ^¶ Medical Technology Department, University of Delaware, Newark, Delaware 19716, and the ^** Instituto de Biomedicina, Consejo Superior de Investigaciones Científicas, Valencia 46010, Spain

There are key differences between the amino acid residues of the RGD loops and the C termini of echistatin, a potent antagonist of _IIb3, _v3 and ₅₁, and eristostatin, a similar disintegrin selectively inhibiting _IIb3. In order to identify echistatin motifs required for selective recognition of _v3 and ₅₁ integrins, we expressed recombinant echistatin, eristostatin, and 15 hybrid molecules. We tested them for their ability to inhibit adhesion of different cell lines to fibronectin and von Willebrand factor and to express ligand-induced binding site epitope. The results showed that Asp²⁷ and Met²⁸ support recognition of both _v3 and ₅₁. Replacement of Met²⁸ with Asn completely abolished echistatin's ability to recognize each of the integrins, while replacement of Met²⁸ with Leu selectively decreased echistatin's ability to recognize ₅₁ only. Eristostatin in which C-terminal WNG sequence was substituted with HKGPAT exhibited new activity with ₅₁, which was 10-20-fold higher than that of wild type eristostatin. A hypothesis is proposed that the C terminus of echistatin interacts with separate sites on ₁ and ₃ integrin molecules.

---

^* This work was supported by National Institutes of Health Training Grant HL 0777 (to I. W. P.), American Heart Association Initial Investigatorship (to M. A. M. and C. M.), and grants-in-aid from the American Heart Association (to S. N.) and Barra Foundation (to S. N.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Present address: Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544. Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Temple University.

To whom correspondence should be addressed: Dept. of Medical Technology, University of Delaware, McKinly Laboratory 057, Newark, DE 19808. Tel.: 302-831-8737; Fax: 302-831-4180; E-mail: mclane@udel.edu.

---

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

This article has been cited by other articles:

				M. Dodig, B. Ogunwale, S. Dasarathy, M. Li, B. Wang, and A. J. McCullough Differences in regulation of type I collagen synthesis in primary and passaged hepatic stellate cell cultures: the role of {alpha}5beta1-integrin Am J Physiol Gastrointest Liver Physiol, July 1, 2007; 293(1): G154 - G164. [Abstract] [Full Text] [PDF]

				R. Sumathipala, C. Xu, J. Seago, A. P. Mould, M. J. Humphries, S. E. Craig, Y. Patel, E. S. Wijelath, M. Sobel, and S. Rahman The "Linker" Region (Amino Acids 38-47) of the Disintegrin Elegantin Is a Novel Inhibitory Domain of Integrin {alpha}5beta1-Dependent Cell Adhesion on Fibronectin: EVIDENCE FOR THE NEGATIVE REGULATION OF FIBRONECTIN SYNERGY SITE BIOLOGICAL ACTIVITY J. Biol. Chem., December 8, 2006; 281(49): 37686 - 37696. [Abstract] [Full Text] [PDF]

				R. R. Hantgan, M. C. Stahle, J. H. Connor, D. A. Horita, M. Rocco, M. A. McLane, S. Yakovlev, and L. Medved Integrin {alpha}IIbbeta3:ligand interactions are linked to binding-site remodeling. Protein Sci., August 1, 2006; 15(8): 1893 - 1906. [Abstract] [Full Text] [PDF]

				P.-L. Wu, S.-C. Lee, C.-C. Chuang, S. Mori, N. Akakura, W.-g. Wu, and Y. Takada Non-cytotoxic Cobra Cardiotoxin A5 Binds to {alpha}vbeta3 Integrin and Inhibits Bone Resorption: IDENTIFICATION OF CARDIOTOXINS AS NON-RGD INTEGRIN-BINDING PROTEINS OF THE Ly-6 FAMILY J. Biol. Chem., March 24, 2006; 281(12): 7937 - 7945. [Abstract] [Full Text] [PDF]

				F. Frausin, V. Scarcia, M. Cocchietto, A. Furlani, B. Serli, E. Alessio, and G. Sava Free Exchange across Cells, and Echistatin-Sensitive Membrane Target for the Metastasis Inhibitor NAMI-A (Imidazolium trans-Imidazole Dimethyl Sulfoxide Tetrachlororuthenate) on KB Tumor Cells J. Pharmacol. Exp. Ther., April 1, 2005; 313(1): 227 - 233. [Abstract] [Full Text] [PDF]

				P. Holig, M. Bach, T. Volkel, T. Nahde, S. Hoffmann, R. Muller, and R. E. Kontermann Novel RGD lipopeptides for the targeting of liposomes to integrin-expressing endothelial and melanoma cells Protein Eng. Des. Sel., May 1, 2004; 17(5): 433 - 441. [Abstract] [Full Text] [PDF]

				D. B. Ellegala, H. Leong-Poi, J. E. Carpenter, A. L. Klibanov, S. Kaul, M. E. Shaffrey, J. Sklenar, and J. R. Lindner Imaging Tumor Angiogenesis With Contrast Ultrasound and Microbubbles Targeted to {alpha}v{beta}3 Circulation, July 22, 2003; 108(3): 336 - 341. [Abstract] [Full Text] [PDF]

				H. Leong-Poi, J. Christiansen, A. L. Klibanov, S. Kaul, and J. R. Lindner Noninvasive Assessment of Angiogenesis by Ultrasound and Microbubbles Targeted to {alpha}v-Integrins Circulation, January 28, 2003; 107(3): 455 - 460. [Abstract] [Full Text] [PDF]

				R. Li, R. H. Hoess, J. S. Bennett, and W. F. DeGrado Use of phage display to probe the evolution of binding specificity and affinity in integrins Protein Eng. Des. Sel., January 1, 2003; 16(1): 65 - 72. [Abstract] [Full Text] [PDF]

				M. Lu, J. S. Munger, M. Steadele, C. Busald, M. Tellier, and L. M. Schnapp Integrin {alpha}8{beta}1 mediates adhesion to LAP-TGF{beta}1 J. Cell Sci., January 12, 2002; 115(23): 4641 - 4648. [Abstract] [Full Text] [PDF]

				Y. Takahashi, D. Bigler, Y. Ito, and J. M. White Sequence-Specific Interaction between the Disintegrin Domain of Mouse ADAM 3 and Murine Eggs: Role of {beta}1 Integrin-associated Proteins CD9, CD81, and CD98 Mol. Biol. Cell, April 1, 2001; 12(4): 809 - 820. [Abstract] [Full Text]

				C. Wild-Bode, M. Weller, A. Rimner, J. Dichgans, and W. Wick Sublethal Irradiation Promotes Migration and Invasiveness of Glioma Cells: Implications for Radiotherapy of Human Glioblastoma Cancer Res., March 1, 2001; 61(6): 2744 - 2750. [Abstract] [Full Text]

				J. H. Paik, S.-s. Chae, M.-J. Lee, S. Thangada, and T. Hla Sphingosine 1-Phosphate-induced Endothelial Cell Migration Requires the Expression of EDG-1 and EDG-3 Receptors and Rho-dependent Activation of alpha vbeta 3- and beta 1-containing Integrins J. Biol. Chem., April 6, 2001; 276(15): 11830 - 11837. [Abstract] [Full Text] [PDF]