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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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Rosado, J. A. Articles by Sage, S. O. Search for Related Content PubMed PubMed Citation Articles by Rosado, J. A. Articles by Sage, S. O. Related Collections Hemostasis, Thrombosis, and Vascular Biology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 May 2001, Vol. 97, No. 9, pp. 2648-2656 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Fibrinogen binding to the integrin IIb3 modulates store-mediated calcium entry in human platelets Juan A. Rosado, Else M. Y. Meijer, Karly Hamulyak, Irena Novakova, Johan W. M. Heemskerk, and Stewart O. Sage From the Department of Physiology, University of Cambridge, Cambridge, United Kingdom; the Departments of Biochemistry and Human Biology, University of Maastricht; the Laboratory of Haematology, Haemostasis Laboratory, Department of Internal Medicine, Academic Hospital Maastricht; and the Department of Haematology, St Radbout Hospital, Nijmegen, The Netherlands. Effects of the occupation of integrin IIb3 by fibrinogen on Ca++ signaling in fura-2-loaded human platelets were investigated. Adding fibrinogen to washed platelet suspensions inhibited increases in cytosolic [Ca++] concentrations ([Ca++]i) evoked by adenosine diphosphate (ADP) and thrombin in a concentration-dependent manner in the presence of external Ca++ but not in the absence of external Ca++ or in the presence of the nonselective cation channel blocker SKF96365, indicating selective inhibition of Ca++ entry. Fibrinogen also inhibited store-mediated Ca++ entry (SMCE) activated after Ca++ store depletion using thapsigargin. The inhibitory effect of fibrinogen was reversed if fibrinogen binding to IIb3 was blocked using RDGS or abciximab and was absent in platelets from patients homozygous for Glanzmann thrombasthenia. Fibrinogen was without effect on SMCE once activated. Activation of SMCE in platelets occurs through conformational coupling between the intracellular stores and the plasma membrane and requires remodeling of the actin cytoskeleton. Fibrinogen inhibited actin polymerization evoked by ADP or thapsigargin in control cells and in cells loaded with the Ca++ chelator dimethyl BAPTA. It also inhibited the translocation of the tyrosine kinase p60src to the cytoskeleton. These results indicate that the binding of fibrinogen to integrin IIb3 inhibits the activation of SMCE in platelets by a mechanism that may involve modulation of the reorganization of the actin cytoskeleton and the cytoskeletal association of p60src. This action may be important in intrinsic negative feedback to prevent the further activation of platelets subjected to low-level stimuli in vivo. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Prevost, J. V. Mitsios, H. Kato, J. E. Burke, E. A. Dennis, T. Shimizu, and S. J. Shattil Group IVA cytosolic phospholipase A2 (cPLA2{alpha}) and integrin {alpha}IIb{beta}3 reinforce each other's functions during {alpha}IIb{beta}3 signaling in platelets Blood, January 8, 2009; 113(2): 447 - 457. [Abstract] [Full Text] [PDF] G. E. Woodard, G. M. Salido, and J. A. 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	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020