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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1643-1650. Prepublished online as a Blood First Edition Paper on October 20, 2005; DOI 10.1182/blood-2005-06-2509. This Article Full Text (PDF) All Versions of this Article: 2005-06-2509v1 107/4/1643    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 Yakubenko, V. P Articles by Ugarova, T. P Search for Related Content PubMed PubMed Citation Articles by Yakubenko, V. P Articles by Ugarova, T. P Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 28, 2005 Accepted October 6, 2005 Integrin D2, an adhesion receptor upregulated on macrophage foam cells, exhibits multiligand binding properties Valentin P Yakubenko, Satya P Yadav, and Tatiana P Ugarova* Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA * Corresponding author; email: ugarovt{at}ccf.org. Integrin D2, the most recently discovered member of the 2 sub-family of integrin adhesion receptors, is upregulated on macrophage foam cells. While other members of the sub-family have been extensively researched, the recognition specificity and the molecular basis for D2, ligand binding remain unknown. Based upon the high extent of structural homology between D2, and the major myeloid cell-specific integrin M2 (Mac-1), noted for its capacity to bind multiple ligands, we considered that the two integrins have similar recognition specificity. In this study, using recombinant and natural D2-expressing cells, we demonstrate that D2, supports adhesion and migration to many extracellular matrix proteins in a fashion similar to M2. Consistent with these data, the recombinant DI-domain of the receptor bound selected ligands. The binding was activation-dependent as the DI-domain with its C-terminal 7 helix truncated, but not the form with the C-terminal part extended, bound ligands. When the DI-domain segment Lys244-Lys260 (highly homologous to its MI-domain counterpart Lys245-Arg261 responsible for M2 multiligand binding properties) was inserted into the monospecific LI-domain, the chimeric protein bound many ligands with affinities similar to those of wild-type DI-domain. These results establish integrin D2 as a multiligand receptor and indicate that the mechanism whereby D2 exhibits broad ligand specificity resembles that utilized by M2, the most promiscuous member of the integrin family. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. M. McKillop, J. W. Barrett, S. H. Pasternak, B. M. C. Chan, and G. A. Dekaban The extracellular domain of CD11d regulates its cell surface expression J. Leukoc. Biol., October 1, 2009; 86(4): 851 - 862. [Abstract] [Full Text] [PDF] S. R. Barthel, M. W. Johansson, D. M. McNamee, and D. F. Mosher Roles of integrin activation in eosinophil function and the eosinophilic inflammation of asthma J. Leukoc. Biol., January 1, 2008; 83(1): 1 - 12. [Abstract] [Full Text] [PDF] Y. Miyazaki, M. Bunting, D. M. Stafforini, E. S. Harris, T. M. McIntyre, S. M. Prescott, V. S. Frutuoso, F. C. Amendoeira, D. de Oliveira Nascimento, A. Vieira-de-Abreu, et al. Integrin {alpha}D 2 Is Dynamically Expressed by Inflamed Macrophages and Alters the Natural History of Lethal Systemic Infections J. Immunol., January 1, 2008; 180(1): 590 - 600. [Abstract] [Full Text] [PDF] V. K. Lishko, T. Burke, and T. Ugarova Antiadhesive effect of fibrinogen: a safeguard for thrombus stability Blood, February 15, 2007; 109(4): 1541 - 1549. [Abstract] [Full Text] [PDF]

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