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Blood, 15 September 2007, Vol. 110, No. 6, pp. 1871-1878. Prepublished online as a Blood First Edition Paper on May 30, 2007; DOI 10.1182/blood-2007-03-081414. This Article Full Text (PDF) All Versions of this Article: blood-2007-03-081414v1 110/6/1871    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 Mancini, F. Articles by Torti, M. Search for Related Content PubMed PubMed Citation Articles by Mancini, F. Articles by Torti, M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 26, 2007 Accepted May 29, 2007 The low molecular weight phosphotyrosine phosphatase is a negative regulator of FcRIIA-mediated cell activation Francesca Mancini, Stefania Rigacci, Andrea Berti, Cesare Balduini, and Mauro Torti* Department of Biochemistry, University of Pavia, Pavia, Italy Department of Biochemical Sciences, University of Florence, Florence, Italy * Corresponding author; email: mtorti{at}unipv.it. Activation of human platelets by cross-linking of the low affinity receptor for immunoglobulin G (FcRIIA) is initiated by Src kinase-mediated phosphorylation of the immunoreceptor tyrosine-based activation motif (ITAM) within the receptor, but the identity of the enzyme responsible for its dephosphorylation and inactivation is unknown. Here we report that the 18 kDa low molecular weight phosphotyrosine phosphatase (LMW-PTP) is expressed in human platelets and undergoes subcellular redistribution upon FcRIIA cross-linking. In vitro, LMW-PTP was found to efficiently dephosphorylate activated FcRIIA and LAT, but not Syk or phospholipase C2. FcR -chain, another ITAM-bearing receptor expressed in platelets, was also a good substrate for LMW-PTP. In the megakaryocytic cell line DAMI, antibody-induced phosphorylation of FcRIIA was rapid and transient. The late dephosphorylation of FcRIIA was dramatically delayed upon reduction of LMW-PTP expression by siRNA. Strikingly, overexpression of LMW-PTP resulted in the inhibition of antibody-induced phosphorylation of FcRIIA, and caused a more rapid dephosphorylation. In addition, overexpression of LMW-PTP inhibited activation of Syk downstream FcRIIA, reduced intracellular Ca2+ mobilization, and impaired the stimulation of protein kinase C. These results demonstrate that LMW-PTP is responsible for FcRIIA dephosphorylation, and is implicated in the downregulation of cell activation mediated by this ITAM-bearing immunoreceptor. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Trifiro, S. A. Williams, Y. Cheli, K. Furihata, F. M. Pulcinelli, D. J. Nugent, and T. J. Kunicki The low-frequency isoform of platelet glycoprotein VIb attenuates ligand-mediated signal transduction but not receptor expression or ligand binding Blood, August 27, 2009; 114(9): 1893 - 1899. [Abstract] [Full Text] [PDF]

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