Phospholipase D1 regulates high-affinity IgE receptor-induced mast cell degranulation
Phospholipase D1 regulates high-affinity IgE receptor-induced mast cell degranulation
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DOI：
10.1182/blood-2004-06-2091
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发表时间：
2004-12-15
期刊：
影响因子：
20.3
通讯作者：
Siraganian, RP
中科院分区：
文献类型：
--
作者：
Hitomi, T;Zhang, J;Siraganian, RP
为了研究磷脂酶 D (PLD) 在 FcepsilonRI 信号传导中的作用，野生型或催化失活形式的 PLD1 或 PLD2 在 RBL-2H3 肥大细胞中稳定过表达。 FcepsilonRI 刺激导致 PLD1 和 PLD2 的激活。然而，PLD1 是大多数受体诱导的 PLD 活性的来源。仅在过表达催化失活的 PLD1 的细胞中，FcepsilonRI 诱导的脱粒作用增强。这种显性失活的 PLD1 增强了 FcepsilonRI 诱导的早期信号分子（例如受体亚基、Sylk 和磷脂酶 C-gamma）的酪氨酸磷酸化，从而导致细胞内 Ca2+ 更快释放。因此，PLD1 负向调节 Ca2+ 反应上游的信号。然而，FcepsilonRI 诱导的 PLD 激活需要 Sylk 并且位于 Ca2+ 反应的下游，这表明基础 PLD1 活性而不是由细胞刺激激活的活性控制了这些早期信号事件。显性失活的 PLD1 减少了未刺激细胞中基础磷脂酸的形成，同时伴随着脂筏内 FcepsilonRI 的增加。这些结果表明，组成型基础 PLD1 活性通过调节磷酸形成来控制由 FcepsilonRI 聚集引发的早期信号，从而导致肥大细胞脱粒。 (C) 2004 年，美国血液学会。
To investigate the role of phospholipase D (PLD) in FcepsilonRI signaling, the wild-type or the catalytically inactive forms of PLD1 or PLD2 were stably overexpressed in RBL-2H3 mast cells. FcepsilonRI 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 FcepsilonRI-induced degranulation only in cells that overexpressed the catalytically inactive PLD1. This dominant-negative PLD1 enhanced FcepsilonRI-induced tyrosine phosphorylations of early signaling molecules such as the receptor subunits, Sylk and phospholipase C-gamma which resulted in faster release of Ca2+ from intracellular sources. Therefore, PLD1 negatively regulates signals upstream of the Ca2+ response. However, FcepsilonRI-induced PLD activation required Sylk 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 FcepsilonRI within the lipid rafts. These results indicate that constitutive basal PLD1 activity by regulating phosphaticlic acid formation controls the early signals initiated by FcepsilonRI aggregation that lead to mast cell degranulation. (C) 2004 by The American Society of Hematology.