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Blood, 15 December 2004, Vol. 104, No. 13, pp. 4122-4128. Prepublished online as a Blood First Edition Paper on August 31, 2004; DOI 10.1182/blood-2004-06-2091. This Article Full Text (PDF) All Versions of this Article: 2004-06-2091v1 104/13/4122    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 Hitomi, T. Articles by Siraganian, R. P Search for Related Content PubMed PubMed Citation Articles by Hitomi, T. Articles by Siraganian, R. P Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 3, 2004 Accepted August 5, 2004 Phospholipase D1 Regulates High Affinity IgE Receptor-Induced Mast Cell Degranulation Tomohiro Hitomi*, Juan Zhang, Liliana M Nicoletti, Ana Cristina G Grodzki, Maria C Jamur, Constance Oliver, and Reuben P Siraganian Receptors and Signal Transduction Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, SP, Brazil * Corresponding author; email: thitomi{at}mail.nih.gov. To investigate the role of phospholipase D (PLD) in FcRI signaling, the wild-type or the catalytically inactive forms of PLD1 or PLD2 were stably overexpressed in RBL-2H3 mast cells. FcRI stimulation resulted in the activation of both PLD1 and PLD2. However, PLD1 was the source of most of receptor-induced PLD activity. There was enhanced FcRI-induced degranulation only in cells that overexpressed the catalytically inactive PLD1. This dominant-negative PLD1 enhanced FcRI-induced tyrosine phosphorylations of early signaling molecules such as the receptor subunits, Syk and phospholipase C- which resulted in faster release of Ca2+ from intracellular sources. Therefore, PLD1 negatively regulates signals upstream of the Ca2+ response. However, FcRI-induced PLD activation required Syk and was downstream of the Ca2+ response, suggesting that basal PLD1 activity rather than that activated by cell stimulation controlled these early signaling events. Dominant-negative PLD1 reduced the basal phosphatidic acid formation in unstimulated cells, which was accompanied by an increase in FcRI within the lipid rafts. These results indicate that constitutive basal PLD1 activity by regulating phosphatidic acid formation controls the early signals initiated by FcRI aggregation that lead to mast cell degranulation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. A. Lisboa, Z. Peng, C. A. Combs, and M. A. Beaven Phospholipase D Promotes Lipid Microdomain-Associated Signaling Events in Mast Cells J. Immunol., October 15, 2009; 183(8): 5104 - 5112. [Abstract] [Full Text] [PDF]

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