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

J. Biol. Chem., Vol. 278, Issue 28, 25808-25815, July 11, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/28/25808    most recent M301534200v1 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 Schober, J. M. Articles by Lam, S. C.-T. Search for Related Content PubMed PubMed Citation Articles by Schober, J. M. Articles by Lam, S. C.-T. Social Bookmarking                      What's this?

Identification of a Novel Integrin _M2 Binding Site in CCN1 (CYR61), a Matricellular Protein Expressed in Healing Wounds and Atherosclerotic Lesions^*

Joseph M. Schober  , Lester F. Lau ¶, Tatiana P. Ugarova || ** and Stephen C.-T. Lam  

From the Departments of Pharmacology and ^¶Molecular Genetics, University of Illinois at Chicago, College of Medicine, Chicago, Illinois 60612 and ^||Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195

CCN1 (cysteine-rich 61) and CCN2 (connective tissue growth factor) are growth factor-inducible immediate-early gene products found in atherosclerotic lesions, restenosed blood vessels, and healing cutaneous wounds. Both CCN proteins have been shown to support cell adhesion and induce cell migration through interaction with integrin receptors. Recently, we have identified integrin _M2 as the major adhesion receptor mediating monocyte adhesion to CCN1 and CCN2 and have shown that the _MI domain binds specifically to both proteins. In the present study, we demonstrated that activated monocytes adhered to a synthetic peptide (CCN1-H2, SSVKKYRPKYCGS) derived from a conserved region within the CCN1 C-terminal domain, and this process was blocked by the anti-_M monoclonal antibody 2LPM19c. Consistently, a glutathione S-transferase (GST) fusion protein containing the _MI domain (GST-_MI) bound to immobilized CCN1-H2 as well as to the corresponding H2 sequence in CCN2 (CCN2-H2, TSVKTYRAKFCGV). By contrast, a scrambled CCN1-H2 peptide and an 18-residue peptide derived from an adjacent sequence of CCN1-H2 failed to support monocyte adhesion or _MI domain binding. To confirm that the CCN1-H2 sequence within the CCN1 protein mediates _M2 interaction, we developed an anti-peptide antibody against CCN1-H2 and showed that it specifically blocked GST-_MI binding to intact CCN1. Collectively, these results identify the H2 sequence in CCN1 and CCN2 as a novel integrin _M2 binding motif that bears no apparent homology to any _M2 binding sequence reported to date.

Received for publication, February 12, 2003 , and in revised form, April 10, 2003.

^* This work was supported by the National Institutes of Health Grants HL-41793 (to S. C.-T. L), CA-46565 and CA-80080 (to L. F. L.), and HL-63199 (to T. P. U.). 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.

Supported by the National Institutes of Health HL-07829 training grant and by a predoctoral fellowship from the American Heart Association, Midwest Affiliate.

^** An Established Investigator of the American Heart Association.

To whom correspondence should be addressed: Dept. of Pharmacology (M/C 868), University of Illinois at Chicago, 835 South Wolcott Ave., Chicago, IL 60612. Tel.: 312-413-5928; Fax: 312-996-1225; E-mail: sclam{at}uic.edu.

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

This article has been cited by other articles:

				H. Matsumae, Y. Yoshida, K. Ono, K. Togi, K. Inoue, Y. Furukawa, Y. Nakashima, Y. Kojima, M. Nobuyoshi, T. Kita, et al. CCN1 Knockdown Suppresses Neointimal Hyperplasia in a Rat Artery Balloon Injury Model Arterioscler. Thromb. Vasc. Biol., June 1, 2008; 28(6): 1077 - 1083. [Abstract] [Full Text] [PDF]

				G. Borland, A. L. Edkins, M. Acharya, J. Matheson, L. J. White, J. M. Allen, J.-Y. Bonnefoy, B. W. Ozanne, and W. Cushley {alpha}vbeta5 Integrin Sustains Growth of Human Pre-B Cells through an RGD-independent Interaction with a Basic Domain of the CD23 Protein J. Biol. Chem., September 14, 2007; 282(37): 27315 - 27326. [Abstract] [Full Text] [PDF]

				M. B. Einarson, E. N. Pugacheva, and J. R. Orlinick Identification of Protein-Protein Interactions with Glutathione-S-Transferase (GST) Fusion Proteins CSH Protocols, July 1, 2007; 2007(16): pdb.top11 - pdb.top11. [Abstract] [Full Text]

				J. Chai, M. Norng, A. S Tarnawski, and J. Chow A critical role of serum response factor in myofibroblast differentiation during experimental oesophageal ulcer healing in rats Gut, May 1, 2007; 56(5): 621 - 630. [Abstract] [Full Text] [PDF]

				A. Leask and D. J. Abraham All in the CCN family: essential matricellular signaling modulators emerge from the bunker J. Cell Sci., December 1, 2006; 119(23): 4803 - 4810. [Abstract] [Full Text] [PDF]

				L. McCallum, S. Price, N. Planque, B. Perbal, A. Pierce, A. D. Whetton, and A. E. Irvine A novel mechanism for BCR-ABL action: stimulated secretion of CCN3 is involved in growth and differentiation regulation Blood, September 1, 2006; 108(5): 1716 - 1723. [Abstract] [Full Text] [PDF]

				R Gao and D R Brigstock A novel integrin {alpha}5{beta}1 binding domain in module 4 of connective tissue growth factor (CCN2/CTGF) promotes adhesion and migration of activated pancreatic stellate cells Gut, June 1, 2006; 55(6): 856 - 862. [Abstract] [Full Text] [PDF]

				V. P. Yakubenko, S. P. Yadav, and T. P. Ugarova Integrin {alpha}Dbeta2, an adhesion receptor up-regulated on macrophage foam cells, exhibits multiligand-binding properties Blood, February 15, 2006; 107(4): 1643 - 1650. [Abstract] [Full Text] [PDF]

				V. K. Lishko, N. P. Podolnikova, V. P. Yakubenko, S. Yakovlev, L. Medved, S. P. Yadav, and T. P. Ugarova Multiple Binding Sites in Fibrinogen for Integrin {alpha}M{beta}2 (Mac-1) J. Biol. Chem., October 22, 2004; 279(43): 44897 - 44906. [Abstract] [Full Text] [PDF]

				N. Chen, S.-J. Leu, V. Todorovic, S. C.-T. Lam, and L. F. Lau Identification of a Novel Integrin {alpha}v{beta}3 Binding Site in CCN1 (CYR61) Critical for Pro-angiogenic Activities in Vascular Endothelial Cells J. Biol. Chem., October 15, 2004; 279(42): 44166 - 44176. [Abstract] [Full Text] [PDF]

				S.-J. Leu, N. Chen, C.-C. Chen, V. Todorovic, T. Bai, V. Juric, Y. Liu, G. Yan, S. C.-T. Lam, and L. F. Lau Targeted Mutagenesis of the Angiogenic Protein CCN1 (CYR61): SELECTIVE INACTIVATION OF INTEGRIN {alpha}6{beta}1-HEPARAN SULFATE PROTEOGLYCAN CORECEPTOR-MEDIATED CELLULAR FUNCTIONS J. Biol. Chem., October 15, 2004; 279(42): 44177 - 44187. [Abstract] [Full Text] [PDF]

				M.-T. Lin, C.-C. Chang, S.-T. Chen, H.-L. Chang, J.-L. Su, Y.-P. Chau, and M.-L. Kuo Cyr61 Expression Confers Resistance to Apoptosis in Breast Cancer MCF-7 Cells by a Mechanism of NF-{kappa}B-dependent XIAP Up-Regulation J. Biol. Chem., June 4, 2004; 279(23): 24015 - 24023. [Abstract] [Full Text] [PDF]

				M. Stefanidakis, M. Bjorklund, E. Ihanus, C. G. Gahmberg, and E. Koivunen Identification of a Negatively Charged Peptide Motif within the Catalytic Domain of Progelatinases That Mediates Binding to Leukocyte {beta}2 Integrins J. Biol. Chem., September 5, 2003; 278(36): 34674 - 34684. [Abstract] [Full Text] [PDF]