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Blood, 15 July 2004, Vol. 104, No. 2, pp. 420-427. Prepublished online as a Blood First Edition Paper on March 30, 2004; DOI 10.1182/blood-2003-08-2881. This Article Full Text (PDF) All Versions of this Article: 2003-08-2881v1 104/2/420    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 Mangin, P. Articles by Lanza, F. Search for Related Content PubMed PubMed Citation Articles by Mangin, P. Articles by Lanza, F. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 21, 2003 Accepted March 16, 2004 Identification of a novel 14-3-3 binding site within the cytoplasmic tail of platelet glycoprotein Ib Pierre Mangin, Tovo David, Vincent Lavaud, Susan L Cranmer, Inna Pikovski, Shaun P Jackson, Michael C Berndt, Jean-Pierre Cazenave, Christian Gachet, and Francois Lanza* INSERM U311-EFS Alsace, Strasbourg, France Dept Medicine, Monash University, Melbourne, Victoria, Australia Dept Biochemistry, Monash University, Clayton, Victoria, Australia * Corresponding author; email: francois.lanza{at}efs-alsace.fr. The glycoprotein (GP) Ib-V-IX complex interacts with subendothelial von Willebrand factor (vWf) to ensure recruitment of platelets at sites of vascular injury, a process which culminates in integrin IIb3-dependent stable adhesion and spreading. Interaction of the 14-3-3 adaptor protein with the C-terminal 606-610 phosphoserine motif of the GPIb subunit has been implicated in the control of IIb3 activation and cell spreading. In this study we have examined potentially novel 14-3-3 binding sites by expressing mutant forms of GPIb in CHO cells. Analysis of a series of neighboring 11-12 residue deletions identified a critical role for the 580-LVAGRRPSALS-590 sequence in promoting GPIb-14-3-3 interaction. Development of a phosphospecific antibody demonstrated high levels of phosphorylation of the Ser-587 and Ser-590 residues in resting platelets (which became dephosphorylated during platelet spreading on vWf), and peptides containing these phosphorylated residues effectively displaced 14-3-3 from GPIb. Analysis of single and double alanine substitutions of Ser-587 and Ser-590 demonstrated a major role for these residues in promoting GPIb-14-3-3 binding. Moreover, these cell lines exhibited a defect in cell spreading on immobilized vWf. These studies demonstrate the existence of a second major 14-3-3 binding site within the cytoplasmic tail of GPIb that has an important functional role in regulating integrin-dependent cell spreading. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F.-T. Mu, R. K. Andrews, J. F. Arthur, A. D. Munday, S. L. Cranmer, S. P. Jackson, F. C. Stomski, A. F. Lopez, and M. C. Berndt A functional 14-3-3{zeta}-independent association of PI3-kinase with glycoprotein Ib{alpha}, the major ligand-binding subunit of the platelet glycoprotein Ib-IX-V complex Blood, May 1, 2008; 111(9): 4580 - 4587. [Abstract] [Full Text] [PDF] N. Y. Tan, V. C. Midgley, M. M. Kavurma, F. S. Santiago, X. Luo, R. Peden, R. G. Fahmy, M. C. Berndt, M. P. Molloy, and L. M. Khachigian Angiotensin II-Inducible Platelet-Derived Growth Factor-D Transcription Requires Specific Ser/Thr Residues in the Second Zinc Finger Region of Sp1 Circ. Res., February 29, 2008; 102(4): e38 - e51. [Abstract] [Full Text] [PDF] G. Garcia-Manero, H. Yang, C. Bueso-Ramos, A. Ferrajoli, J. Cortes, W. G. Wierda, S. Faderl, C. Koller, G. Morris, G. Rosner, et al. Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes Blood, February 1, 2008; 111(3): 1060 - 1066. [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] 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]

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