Phospholipase D1 regulates high-affinity IgE receptor-induced mast cell degranulation

Tomohiro Hitomi, Juan Zhang, Liliana M. Nicoletti, Ana Grodzki, Maria C. Jamur, Constance Oliver, Reuben P. Siraganian

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

To investigate the role of phospholipase D (PLD) in FcεRI signaling, the wild-type or the catalytically inactive forms of PLD1 or PLD2 were stably overexpressed in RBL-2H3 mast cells. FcεRI stimulation resulted in the activation of both PLD1 and PLD2. However, PLD1 was the source of most of the receptor-induced PLD activity. There was enhanced FcεRI-induced degranulation only in cells that overexpressed the catalytically inactive PLD1. This dominant-negative PLD1 enhanced FcεRI-induced tyrosine phosphorylations of early signaling molecules such as the receptor subunits, Syk and phospholipase C-γ which resulted in faster release of Ca2+ from intracellular sources. Therefore, PLD1 negatively regulates signals upstream of the Ca2+ response. However, FcεRi-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 FcεRI within the lipid rafts. These results indicate that constitutive basal PLD1 activity by regulating phosphatidic acid formation controls the early signals initiated by FcεRI aggregation that lead to mast cell degranulation.

Original languageEnglish (US)
Pages (from-to)4122-4128
Number of pages7
JournalBlood
Volume104
Issue number13
DOIs
StatePublished - Dec 15 2004
Externally publishedYes

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ASJC Scopus subject areas

  • Hematology

Cite this

Hitomi, T., Zhang, J., Nicoletti, L. M., Grodzki, A., Jamur, M. C., Oliver, C., & Siraganian, R. P. (2004). Phospholipase D1 regulates high-affinity IgE receptor-induced mast cell degranulation. Blood, 104(13), 4122-4128. https://doi.org/10.1182/blood-2004-06-2091