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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-08-2529. This Article Full Text (PDF) All Versions of this Article: 2002-08-2529v1 101/5/1790    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 Lee, G. Articles by Chasis, J. A Search for Related Content PubMed PubMed Citation Articles by Lee, G. Articles by Chasis, J. A Social Bookmarking                   What's this? Submitted August 16, 2002 Accepted October 4, 2002 Novel secreted isoform of adhesion molecule ICAM-4: potential regulator of membrane-associated ICAM-4 interactions Gloria Lee, Frances A Spring, Stephen F Parsons, Tosti J Mankelow, Luanne L Peters, Mark J Koury, Mohandas Narla, David J Anstee, and Joel A Chasis* Life Sciences Division, University of California Lawrence Berkeley National Laboratory, Berkeley, CA, USA The Bristol Institute for Transfusion Sciences, Bristol, United Kingdom The Jackson Laboratory, Bar Harbor, ME, USA Vanderbilt University, Nashville, TN, USA The New York Blood Center, New York, NY, USA * Corresponding author; email: jachasis{at}lbl.gov. ICAM-4, a newly characterized adhesion molecule, is expressed early in human erythropoiesis and functions as a ligand for binding 4ß1 and V integrin-expressing cells. Within the bone marrow, erythroblasts surround central macrophages forming erythroblastic islands. Evidence suggests that these islands are highly specialized subcompartments where cell adhesion events, in concert with cytokines, play critical roles in regulating erythropoiesis and apoptosis. Since erythroblasts express 4ß1 and ICAM-4 and macrophages exhibit V, ICAM-4 is an attractive candidate for mediating cellular interactions within erythroblastic islands. To determine whether ICAM-4 binding properties are conserved across species, we first cloned and sequenced the murine homologue. The translated amino acid sequence showed 68% overall identity with human ICAM-4. Using recombinant murine ICAM-4 extracellular domains, we discovered that hematopoietic 4ß1-expressing HEL cells and non-hematopoietic V-expressing FLY cells adhered to mouse ICAM-4. Cell adhesion studies showed that FLY and HEL cells bound to mouse and human proteins with similar avidity. These data strongly suggest conservation of integrin-binding properties across species. Importantly, we characterized a novel second splice cDNA that would be predicted to encode an ICAM-4 isoform, lacking the membrane-spanning domain. Erythroblasts express both isoforms of ICAM-4. COS-7 cells transfected with GFP constructs of prototypic or novel ICAM-4 cDNA showed different cellular localization patterns. Moreover, analysis of tissue culture medium revealed that the novel ICAM-4 cDNA encodes a secreted protein. We postulate that secretion of this newly described isoform, ICAM-4S, may modulate binding of membrane-associated ICAM-4 and could thus play a critical regulatory role in erythroblast molecular attachments. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. A. Chasis and N. Mohandas Erythroblastic islands: niches for erythropoiesis Blood, August 1, 2008; 112(3): 470 - 478. [Abstract] [Full Text] [PDF] A. A. Lamikanra, D. Brown, A. Potocnik, C. Casals-Pascual, J. Langhorne, and D. J. Roberts Malarial anemia: of mice and men Blood, July 1, 2007; 110(1): 18 - 28. [Abstract] [Full Text] [PDF] E. Ihanus, L. M. Uotila, A. Toivanen, M. Varis, and C. G. Gahmberg Red-cell ICAM-4 is a ligand for the monocyte/macrophage integrin CD11c/CD18: characterization of the binding sites on ICAM-4 Blood, January 15, 2007; 109(2): 802 - 810. [Abstract] [Full Text] [PDF] G. Lee, A. Lo, S. A. Short, T. J. Mankelow, F. Spring, S. F. Parsons, K. Yazdanbakhsh, N. Mohandas, D. J. Anstee, and J. A. Chasis Targeted gene deletion demonstrates that the cell adhesion molecule ICAM-4 is critical for erythroblastic island formation Blood, September 15, 2006; 108(6): 2064 - 2071. [Abstract] [Full Text] [PDF] J. L. Ponthier, C. Schluepen, W. Chen, R. A. Lersch, S. L. Gee, V. C. Hou, A. J. Lo, S. A. Short, J. A. Chasis, J. C. Winkelmann, et al. Fox-2 Splicing Factor Binds to a Conserved Intron Motif to Promote Inclusion of Protein 4.1R Alternative Exon 16 J. Biol. Chem., May 5, 2006; 281(18): 12468 - 12474. [Abstract] [Full Text] [PDF] T. J. Mankelow, F. A. Spring, S. F. Parsons, R. L. Brady, N. Mohandas, J. A. Chasis, and D. J. Anstee Identification of critical amino-acid residues on the erythroid intercellular adhesion molecule-4 (ICAM-4) mediating adhesion to {alpha}V integrins Blood, February 15, 2004; 103(4): 1503 - 1508. [Abstract] [Full Text] [PDF]

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