HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 37, 25514-25523, September 12, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/37/25514    most recent M705320200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Amir-Moazami, O. Articles by Benhamou, M. Search for Related Content PubMed PubMed Citation Articles by Amir-Moazami, O. Articles by Benhamou, M. Social Bookmarking                      What's this?

Phospholipid Scramblase 1 Modulates a Selected Set of IgE Receptor-mediated Mast Cell Responses through LAT-dependent Pathway^*

From the INSERM U699, and Université Paris 7, FacultédeMédecine Xavier Bichat, 16 Rue Henri Huchard, F-75018 Paris, France

Engagement of the IgE receptor (FcRI) on mast cells leads to the release of preformed and newly formed mediators as well as of cytokines. The signaling pathways responsible for these responses involve tyrosine phosphorylation of multiple proteins. We previously reported the phosphorylation on tyrosine of phospholipid scramblase 1 (PLSCR1) after FcRI aggregation. Here, PLSCR1 expression was knocked down in the RBL-2H3 mast cell line using short hairpin RNA. Knocking down PLSCR1 expression resulted in significantly impaired degranulation responses after FcRI aggregation and release of vascular endothelial growth factor, whereas release of MCP-1 was minimally affected. The release of neither leukotriene C4 nor prostaglandin D2 was altered by knocking down of PLSCR1. Analysis of FcRI-dependent signaling pathways revealed that whereas tyrosine phosphorylation of ERK and Akt was unaffected, tyrosine phosphorylation of LAT was significantly reduced in PLSCR1 knocked down cells. Tyrosine phosphorylation of phospholipase C1 and consequently the mobilization of calcium were also significantly reduced in these cells. In nonactivated mast cells, PLSCR1 was found in part in lipid rafts where it was further recruited after cell activation and was constitutively associated with Lyn and Syk but not with LAT or Fyn. Altogether, these data identify PLSCR1 as a novel amplifier of FcRI signaling that acts selectively on the Lyn-initiated LAT/phospholipase C1/calcium axis, resulting in potentiation of a selected set of mast cell responses.

Received for publication, June 28, 2007 , and in revised form, May 21, 2008.

^* This work was supported in part by Association pour l'Utilisation du Rein Artificiel and by Grant 2002004544 (to M. B.) from the Fondation de France. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S6.

¹ Supported by a Ministére de l' Enseignement Supérieur et de la Recherche grant. Present address: Dep. of Internal Medicine, Washington University, 660 S. Euclid Ave., Saint Louis, MO 63110.

² Both authors contributed equally to this work.

³ Supported by Grant DAL20041203160 from the Fondation pour la Recherche Médicale.

⁴ Supported by a grant from the Ligue Nationale Contre le Cancer and by a Ministére de l' Enseignement Supérieur et de la Recherche grant.

⁵ To whom correspondence should be addressed: INSERM U699, Facultéde Médecine Xavier Bichat, 16 Rue Henri Huchard, 75018 Paris, France. Tel.: 33-1-5727-7519; Fax: 33-1-5727-7661; E-mail: Marc.Benhamou{at}inserm.fr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Bateman, R. D. Finn, P. J. Sims, T. Wiedmer, A. Biegert, and J. Soding Phospholipid scramblases and Tubby-like proteins belong to a new superfamily of membrane tethered transcription factors Bioinformatics, January 15, 2009; 25(2): 159 - 162. [Abstract] [Full Text] [PDF]