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Blood, 1 December 2005, Vol. 106, No. 12, pp. 3816-3823. Prepublished online as a Blood First Edition Paper on August 4, 2005; DOI 10.1182/blood-2005-03-0911. This Article Full Text (PDF) All Versions of this Article: 2005-03-0911v1 106/12/3816    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 Wee, J. L Articles by Jackson, D. E Search for Related Content PubMed PubMed Citation Articles by Wee, J. L Articles by Jackson, D. E Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 7, 2005 Accepted July 31, 2005 The Ig-ITIM superfamily member, PECAM-1 regulates the 'outside-in' signalling properties of integrin IIb3 in platelets Janet L Wee and Denise E Jackson* Kronheimer Building, Austin Research Institute, Austin Health, Heidelberg, Victoria, Australia * Corresponding author; email: d.jackson{at}ari.unimelb.edu.au. Previous studies have implicated that the Ig-ITIM superfamily member, PECAM-1 may regulate integrin function. While PECAM-1 has been demonstrated to play a role as an inhibitory co-receptor of ITAM-associated FcRIIa and GPVI/FcR -chain signalling pathways in platelets, its physiologic role in integrin IIb3-mediated platelet function is unclear. In this study, we investigate the functional importance of PECAM-1 in murine platelets. Using PECAM-1-deficient mice, we show that the platelets have impaired 'outside-in' integrin IIb3 signalling with impaired platelet spreading on fibrinogen, failure to retract fibrin clots in vitro and reduced tyrosine phosphorylation of 125FAK following integrin IIb3-mediated platelet aggregation. This functional integrin IIb3 defect could not be attributed to altered expression of integrin IIb3. PECAM-1-/- platelets displayed normal platelet alpha granule secretion, normal platelet aggregation to PAR-4, ADP and calcium ionophore and static platelet adhesion. In addition, PECAM-1-/- platelets displayed normal 'inside out' integrin IIb3 signalling properties as demonstrated by normal agonist-induced binding of soluble FITC fibrinogen, JON/A antibody binding, increases in cytosolic free calcium and IP3 levels. This study provides direct evidence that PECAM-1 is essential for normal integrin IIb3-mediated platelet function and that disruption of PECAM-1 induced a moderate 'outside-in' integrin IIb3 signalling defect. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Cao, M. L. Fehrenbach, J. T. Williams, J. M. Finklestein, J.-X. Zhu, and H. M. DeLisser Angiogenesis in Platelet Endothelial Cell Adhesion Molecule-1-Null Mice Am. J. Pathol., August 1, 2009; 175(2): 903 - 915. [Abstract] [Full Text] [PDF] K. Izawa, J. Kitaura, Y. Yamanishi, T. Matsuoka, A. Kaitani, M. Sugiuchi, M. Takahashi, A. Maehara, Y. Enomoto, T. Oki, et al. An Activating and Inhibitory Signal from an Inhibitory Receptor LMIR3/CLM-1: LMIR3 Augments Lipopolysaccharide Response through Association with FcR{gamma} in Mast Cells J. Immunol., July 15, 2009; 183(2): 925 - 936. [Abstract] [Full Text] [PDF] J. Rivera, M. L. Lozano, L. 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