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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3263-3270. Prepublished online as a Blood First Edition Paper on August 10, 2007; DOI 10.1182/blood-2007-07-100453. This Article Full Text (PDF) All Versions of this Article: blood-2007-07-100453v1 110/9/3263    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 Jiang, Y. Articles by Boyce, J. A. Search for Related Content PubMed PubMed Citation Articles by Jiang, Y. Articles by Boyce, J. A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 10, 2007 Accepted August 8, 2007 CysLT2 receptors interact with CysLT1 receptors and down-modulate cysteinyl leukotriene-dependent mitogenic responses of mast cells Yongfeng Jiang, Laura A. Borrelli, Yoshihide Kanaoka, Brian J. Bacskai, and Joshua A. Boyce* Department of Medicine, Harvard Medical School, Boston, MA, United States MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Boston, MA, United States Division of Rheumatology, Immunology & Allergy, Brigham and Women's Hospital, Boston, MA, United States Department of Pediatrics, Harvard Medical School, Boston, MA, United States * Corresponding author; email: jboyce{at}rics.bwh.harvard.edu. Cysteinyl leukotrienes (cys-LTs) induce inflammation through two G protein-coupled receptors (GPCRs), CysLT1 and CysLT2, which are co-expressed by most myeloid cells. Cys-LTs induce proliferation of mast cells (MCs), transactivate c-Kit, and phosphorylate extracellular signal-regulated kinase (ERK). Although MCs express CysLT2, their responses to cys-LTs are blocked by antagonists of CysLT1. We demonstrate that CysLT2 interacts with CysLT1, and that knock-down of CysLT2 increases CysLT1 surface expression and CysLT1-dependent proliferation of cord blood-derived human MCs (hMCs). Cys-LT-mediated responses were absent in MCs from mice lacking CysLT1 receptors, but enhanced by the absence of CysLT2 receptors. CysLT1 and CysLT2 receptors co-localized to the plasma membranes and nuclei of a human MC line, LAD2. Antibody-based fluorescent lifetime imaging microscopy confirmed complexes containing both receptors based on fluorescence energy transfer. Negative regulation of CysLT1-induced mitogenic signaling responses of MCs by CysLT2 demonstrates physiologically relevant functions for GPCR heterodimers on primary cells central to inflammation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Paruchuri, Y. Jiang, C. Feng, S. A. Francis, J. Plutzky, and J. A. Boyce Leukotriene E4 Activates Peroxisome Proliferator-activated Receptor {gamma} and Induces Prostaglandin D2 Generation by Human Mast Cells J. Biol. Chem., June 13, 2008; 283(24): 16477 - 16487. [Abstract] [Full Text] [PDF]

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