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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3322-3329. Prepublished online as a Blood First Edition Paper on December 21, 2004; DOI 10.1182/blood-2004-07-2881. This Article Full Text (PDF) All Versions of this Article: 2004-07-2881v1 105/8/3322    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 Murphy, M. M Articles by Parise, L. V Search for Related Content PubMed PubMed Citation Articles by Murphy, M. M Articles by Parise, L. V Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 27, 2004 Accepted December 10, 2004 Role of Rap1 in promoting sickle red blood cell adhesion to laminin via BCAM/LU Meghan M Murphy, Mohamed A Zayed, Allyson Evans, Carol E Parker, Kenneth I Ataga, Marilyn J Telen, and Leslie V Parise* Department of Pharmacology, University of North Carolina, Chapel Hill, NC, USA Department of Biochemistry, University of North Carolina, Chapel Hill, NC, USA Department of Medicine, University of North Carolina, Chapel Hill, NC, USA Department of Medicine, Duke University, Durham, NC, USA * Corresponding author; email: parise{at}med.unc.edu. Vasoocclusion is a hallmark of sickle cell disease. Agonist-induced activation of sickle red blood cells (SS RBCs) promotes their adhesion to vascular proteins, potentially contributing to vasoocclusion. Previously, we described a cAMP-dependent increase in SS RBC adhesion to laminin. Here, we investigated whether Rap1, a small GTPase known to promote integrin-mediated adhesion in other cells, was involved in this signaling pathway. We found that agonists known to induce cAMP signaling promoted the GTP-bound, active state of Rap1 in SS RBCs. The cAMP-dependent exchange factor Epac is a likely upstream activator of Rap1, since Epac is present in these cells and the Epac-specific cAMP analog, 8CPT-2-Me, activated Rap1 and promoted SS RBC adhesion to laminin. This 8CPT-2-Me-stimulated adhesion was integrin-independent, since it was insensitive to RGD peptide or antibodies against the only known integrin on SS RBCs, 41. However, this adhesion was completely inhibited by either a soluble version of BCAM/LU or a BCAM/LU adhesion-blocking antibody. Surprisingly, 8CPT-2-Me-activated Rap1 did not promote SS RBC adhesion to a known 41 ligand, VCAM-1. These results demonstrate that Epac-induced Rap1 activation in SS RBCs promotes BCAM/LU-mediated adhesion to laminin. Thus, Epac-mediated Rap1 activation may represent an important signaling pathway for promoting SS RBC adhesion. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: The sticking point Narla Mohandas Blood 2005 105: 3008-3009. [Full Text] [PDF] This article has been cited by other articles: M.-H. Odievre, V. Bony, M. Benkerrou, C. Lapoumeroulie, C. Alberti, R. Ducrocq, E. Jacqz-Aigrain, J. Elion, and J.-P. Cartron Modulation of erythroid adhesion receptor expression by hydroxyurea in children with sickle cell disease Haematologica, April 1, 2008; 93(4): 502 - 510. [Abstract] [Full Text] [PDF] T. J. Mankelow, N. Burton, F. O. Stefansdottir, F. A. Spring, S. F. Parsons, J. S. Pedersen, C. L. P. Oliveira, D. Lammie, T. Wess, N. Mohandas, et al. The Laminin 511/521 binding site on the Lutheran blood group glycoprotein is located at the flexible junction of Ig domains 2 and 3 Blood, November 1, 2007; 110(9): 3398 - 3406. [Abstract] [Full Text] [PDF] Y. Kikkawa, T. Sasaki, M. T. Nguyen, M. Nomizu, T. Mitaka, and J. H. Miner The LG1-3 Tandem of Laminin {alpha}5 Harbors the Binding Sites of Lutheran/Basal Cell Adhesion Molecule and {alpha}3beta1/{alpha}6beta1 Integrins J. Biol. Chem., May 18, 2007; 282(20): 14853 - 14860. [Abstract] [Full Text] [PDF] W. El Nemer, M.-P. Wautier, C. Rahuel, P. Gane, P. Hermand, F. Galacteros, J.-L. Wautier, J.-P. Cartron, Y. Colin, and C. Le Van Kim Endothelial Lu/BCAM glycoproteins are novel ligands for red blood cell {alpha}4{beta}1integrin: role in adhesion of sickle red blood cells to endothelial cells Blood, April 15, 2007; 109(8): 3544 - 3551. [Abstract] [Full Text] [PDF] M. J. 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