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Prepublished online as a Blood First Edition Paper on June 5, 2003; DOI 10.1182/blood-2002-12-3805. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-12-3805v1 102/6/2122    most recent 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 Feng, S. Articles by Kroll, M. H. Search for Related Content PubMed PubMed Citation Articles by Feng, S. Articles by Kroll, M. H. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Cytoskeleton Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 September 2003, Vol. 102, No. 6, pp. 2122-2129 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Filamin A binding to the cytoplasmic tail of glycoprotein Ib regulates von Willebrand factor–induced platelet activation Shuju Feng, Julio C. Reséndiz, Xin Lu, and Michael H. Kroll From the Section of Thrombosis Research, VA Medical Center; the Department of Medicine, Baylor College of Medicine; and the Department of Biomedical Engineering, Rice University, Houston, TX; and Wihuri Research Institute, Helsinki, Finland. We examined the hypothesis that filamin A binding to the cytoplasmic tail of platelet glycoprotein Ib (GpIb) is regulated by pathologic shear stress and modulates von Willebrand factor (VWF)–induced platelet activation. To begin, we examined filamin binding to GpIb in Chinese hamster ovary cells coexpressing mutant human GpIb-IX and wild-type human filamin A. We observed that many different deletions and truncations N-terminal to GpIb's cytoplasmic domain residue 594 disrupted filamin A binding, but that binding was unaffected by 14 different point mutations in hydrophilic residues between amino acids 557 and 593. To try to narrow GpIb's filamin A–binding domain, we next measured the effect of several cytoplasmic domain peptides on human filamin A binding to a GST-GpIb cytoplasmic domain fusion protein. One peptide (residues 557-575; designated "A4 peptide") inhibited filamin A binding to the GST-GpIb cytoplasmic domain fusion protein and competed with GpIb for binding to filamin A. When the A4 peptide was delivered to intact human platelets using a carrier peptide, we observed the dose-dependent inhibition of VWF-induced platelet aggregation in response to both ristocetin and shear stress. The effect of the A4 peptide on shear-induced platelet aggregation was accompanied by the attenuation of shear-induced filamin A binding to GpIb and diminished shear-dependent protein tyrosine phosphorylation. These results suggest that shear-dependent VWF-induced platelet activation affects filamin A binding to GpIb-IX-V, and that filamin A binding to the cytoplasmic tail of GpIb regulates proaggregatory tyrosine kinase signaling. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: GPIb, filamin, and platelet activation: a view from within Susan L. Cranmer and Shaun P. Jackson Blood 2003 102: 1937. [Full Text] [PDF] This article has been cited by other articles: L.-J. Armstrong, V. L. Heath, S. Sanderson, S. Kaur, J. F.J. Beesley, J. M.J. Herbert, J. A. Legg, R. Poulsom, and R. Bicknell ECSM2, An Endothelial Specific Filamin A Binding Protein That Mediates Chemotaxis Arterioscler Thromb Vasc Biol, September 1, 2008; 28(9): 1640 - 1646. [Abstract] [Full Text] [PDF] A. Fontayne, B. De Maeyer, M. De Maeyer, M. Yamashita, T. Matsushita, and H. Deckmyn Paratope and Epitope Mapping of the Antithrombotic Antibody 6B4 in Complex with Platelet Glycoprotein Ib{alpha} J. Biol. Chem., August 10, 2007; 282(32): 23517 - 23524. [Abstract] [Full Text] [PDF] S.-Z. Luo, X. Mo, V. Afshar-Kharghan, S. Srinivasan, J. A. Lopez, and R. Li Glycoprotein Ib{alpha} forms disulfide bonds with 2 glycoprotein Ib{beta} subunits in the resting platelet Blood, January 15, 2007; 109(2): 603 - 609. [Abstract] [Full Text] [PDF] S. Feng, X. Lu, J. C. Resendiz, and M. H. Kroll Pathological shear stress directly regulates platelet {alpha}IIbbeta3 signaling Am J Physiol Cell Physiol, December 1, 2006; 291(6): C1346 - C1354. [Abstract] [Full Text] [PDF] M. C. Berndt, S. L. Cranmer, and R. K. Andrews Filamin A interaction with GPIb{alpha}: the platelet shapes up Blood, March 1, 2006; 107(5): 1745 - 1745. [Full Text] [PDF] F. Nakamura, R. Pudas, O. Heikkinen, P. Permi, I. Kilpelainen, A. D. Munday, J. H. Hartwig, T. P. Stossel, and J. Ylanne The structure of the GPIb-filamin A complex Blood, March 1, 2006; 107(5): 1925 - 1932. [Abstract] [Full Text] [PDF] S. Feng, X. Lu, and M. H. Kroll Filamin Binding to Glycoprotein Ib{alpha} Signals Talin-Directed {alpha} IIb{beta} 3 Activation. Blood (ASH Annual Meeting Abstracts), November 16, 2005; 106(11): 383 - 383. [Abstract] K. Dai, R. Bodnar, M. C. Berndt, and X. Du A critical role for 14-3-3{zeta} protein in regulating the VWF binding function of platelet glycoprotein Ib-IX and its therapeutic implications Blood, September 15, 2005; 106(6): 1975 - 1981. [Abstract] [Full Text] [PDF] S. Feng, X. Lu, and M. H. Kroll Filamin A Binding Stabilizes Nascent Glycoprotein Ib{alpha} Trafficking and Thereby Enhances Its Surface Expression J. Biol. Chem., February 25, 2005; 280(8): 6709 - 6715. [Abstract] [Full Text] [PDF] C. Oury, E. Sticker, H. Cornelissen, R. De Vos, J. Vermylen, and M. F. Hoylaerts ATP Augments von Willebrand Factor-dependent Shear-induced Platelet Aggregation through Ca2+-Calmodulin and Myosin Light Chain Kinase Activation J. Biol. Chem., June 18, 2004; 279(25): 26266 - 26273. [Abstract] [Full Text] [PDF]

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