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

J. Biol. Chem., Vol. 279, Issue 47, 49177-49187, November 19, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/47/49177    most recent M404730200v1 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 Furumoto, Y. Articles by Ra, C. Search for Related Content PubMed PubMed Citation Articles by Furumoto, Y. Articles by Ra, C. Social Bookmarking                      What's this?

The FcRI Immunoreceptor Tyrosine-based Activation Motif Exerts Inhibitory Control on MAPK and IB Kinase Phosphorylation and Mast Cell Cytokine Production^*

Yasuko Furumoto, Satoshi Nunomura, Tomoyoshi Terada, Juan Rivera¶||, and Chisei Ra||

From the Molecular Inflammation Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892 and Division of Molecular Cell Immunobiology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, 30-1 Oyaguchi-Kamimachi, Itabashi-ku, Tokyo, 137-8610, Japan

The high affinity IgE Fc receptor (FcRI) chain functions as a signal amplifier and has been linked to atopy, asthma, and allergy. Herein, we report on a previously unrecognized negative regulatory role for the nonconventional chain immunoreceptor tyrosine-based activation motif that contains three tyrosine residues (YX₅YX₃Y). Degranulation and leukotriene production was found to be impaired in cells expressing the mutated FcRI immunoreceptor tyrosine-based activation motifs FYY, YYF, FYF, and FFF. In contrast, cytokine synthesis and secretion were enhanced in the YFY and FFF mutants. FcRI phosphorylation and Lyn kinase co-immunoprecipitation was intact in the YFY mutant but was lost in the FYF and FFF mutants. The phosphorylation of Syk, LAT, phospholipase 1/2, and Srchomology 2 domain-containing protein phosphatase 2 was intact, whereas the phosphorylation of SHIP-1 was significantly reduced in the YFY mutant cells. The FYF and FFF mutants were defective in phosphorylating all of these molecules. In contrast, the phosphorylation of ERK, p38 MAPK, IB kinase (IKK), and nuclear NFB activity was enhanced in the YFY and FFF mutants. These findings show that the FcRI functions to both selectively amplify (degranulation and leukotriene secretion) and dampen (lymphokine) mast cell effector responses.

Received for publication, April 28, 2004 , and in revised form, September 7, 2004.

^* This work was supported by the Department of Health and Human Services, NIAMS, National Institutes of Health (to J. R.) and United States-Israel Bi-national Science Foundation Grant 2000016 (to J. R.) and a fellowship (to Y. F.) from the Japan Society for Promotion of Science. 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.

^|| Both authors contributed equally to this work.

^¶ To whom correspondence should be addressed: NIAMS, National Institutes of Health, Bldg. 10, Rm. 9N228, Bethesda, MD 20892-1820. Tel.: 301-496-7592; Fax: 301-480-1580; E-mail: juan_rivera{at}nih.gov.

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

This article has been cited by other articles:

				T. Yamashita, R. Suzuki, P. S. Backlund, Y. Yamashita, A. L. Yergey, and J. Rivera Differential Dephosphorylation of the FcR{gamma} Immunoreceptor Tyrosine-based Activation Motif Tyrosines with Dissimilar Potential for Activating Syk J. Biol. Chem., October 17, 2008; 283(42): 28584 - 28594. [Abstract] [Full Text] [PDF]

				K. Nakata, T. Yoshimaru, Y. Suzuki, T. Inoue, C. Ra, H. Yakura, and K. Mizuno Positive and Negative Regulation of High Affinity IgE Receptor Signaling by Src Homology Region 2 Domain-Containing Phosphatase 1 J. Immunol., October 15, 2008; 181(8): 5414 - 5424. [Abstract] [Full Text] [PDF]

				H. Peterfy, G. Toth, I. Pecht, and A. Erdei C3a-derived peptide binds to the type I Fc{varepsilon}R and inhibits proximal-coupling signal processes and cytokine secretion by mast cells Int. Immunol., October 1, 2008; 20(10): 1239 - 1245. [Abstract] [Full Text] [PDF]

				K. Roget, M. Malissen, O. Malbec, B. Malissen, and M. Daeron Non-T Cell Activation Linker Promotes Mast Cell Survival by Dampening the Recruitment of SHIP1 by Linker for Activation of T Cells J. Immunol., March 15, 2008; 180(6): 3689 - 3698. [Abstract] [Full Text] [PDF]

				H. Hong, J. Kitaura, W. Xiao, V. Horejsi, C. Ra, C. A. Lowell, Y. Kawakami, and T. Kawakami The Src family kinase Hck regulates mast cell activation by suppressing an inhibitory Src family kinase Lyn Blood, October 1, 2007; 110(7): 2511 - 2519. [Abstract] [Full Text] [PDF]

				W.-H. Leung and S. Bolland The Inositol 5'-Phosphatase SHIP-2 Negatively Regulates IgE-Induced Mast Cell Degranulation and Cytokine Production J. Immunol., July 1, 2007; 179(1): 95 - 102. [Abstract] [Full Text] [PDF]

				G. H. Boekhoudt, M. R. Frazier-Jessen, and G. M. Feldman Immune complexes suppress IFN-{gamma} signaling by activation of the Fc{gamma}RI pathway J. Leukoc. Biol., April 1, 2007; 81(4): 1086 - 1092. [Abstract] [Full Text] [PDF]

				K. Takahashi, N. Hayashi, S. Kaminogawa, and C. Ra Molecular Mechanisms for Transcriptional Regulation of Human High-Affinity IgE Receptor beta-Chain Gene Induced by GM-CSF J. Immunol., October 1, 2006; 177(7): 4605 - 4611. [Abstract] [Full Text] [PDF]

				C. M. Udell, L. A. Samayawardhena, Y. Kawakami, T. Kawakami, and A. W. B. Craig Fer and Fps/Fes Participate in a Lyn-dependent Pathway from Fc{epsilon}RI to Platelet-Endothelial Cell Adhesion Molecule 1 to Limit Mast Cell Activation J. Biol. Chem., July 28, 2006; 281(30): 20949 - 20957. [Abstract] [Full Text] [PDF]

				M. Kovarova, C. A. Wassif, S. Odom, K. Liao, F. D. Porter, and J. Rivera Cholesterol deficiency in a mouse model of Smith-Lemli-Opitz syndrome reveals increased mast cell responsiveness J. Exp. Med., May 15, 2006; 203(5): 1161 - 1171. [Abstract] [Full Text] [PDF]

				W. Xiao, H. Nishimoto, H. Hong, J. Kitaura, S. Nunomura, M. Maeda-Yamamoto, Y. Kawakami, C. A. Lowell, C. Ra, and T. Kawakami Positive and Negative Regulation of Mast Cell Activation by Lyn via the Fc{epsilon}RI J. Immunol., November 15, 2005; 175(10): 6885 - 6892. [Abstract] [Full Text] [PDF]

				S. Nunomura, Y. Gon, T. Yoshimaru, Y. Suzuki, H. Nishimoto, T. Kawakami, and C. Ra Role of the Fc{epsilon}RI {beta}-chain ITAM as a signal regulator for mast cell activation with monomeric IgE Int. Immunol., June 1, 2005; 17(6): 685 - 694. [Abstract] [Full Text] [PDF]