Phospholipase Cγ1 Connects the Cell Membrane Pathway to the Nuclear Receptor Pathway in Insect Steroid Hormone Signaling
Phospholipase Cγ1 Connects the Cell Membrane Pathway to the Nuclear Receptor Pathway in Insect Steroid Hormone Signaling
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磷脂酶 C gamma 1 将昆虫类固醇激素信号传导中的细胞膜通路与核受体通路连接起来
DOI：
10.1074/jbc.m113.547018
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发表时间：
2014-05-09
影响因子：
4.8
通讯作者：
Zhao, Xiao-Fan
中科院分区：
文献类型：
--
作者：
Liu, Wen;Cai, Mei-Juan;Zhao, Xiao-Fan
背景：PLCG 1在钙信号转导中起重要作用。结果：PLCG 1上调20 E诱导的Ca ~（2+）信号通路，并调节棉铃虫体内USP 1蛋白激酶C的磷酸化。结论：20 E通过激活PLCG 1诱导钙内流，调节USP 1蛋白激酶C磷酸化，促进基因表达。重要性：我们的研究建立了类固醇激素20 E信号转导的非基因组途径和基因组途径之间的联系，除了经典的核受体途径外，在动物类固醇激素信号转导的细胞膜中还存在一条非基因组途径调节基因表达，但其机制尚不清楚。在这里，我们报告，昆虫类固醇激素20-羟基蜕皮激素（20 E）调节钙内流通过磷脂酶C1（PLCG 1）调节蛋白激酶C磷酸化的转录因子超气门（USP 1）在鳞翅目昆虫棉铃虫。PLCG 1 mRNA水平在蜕皮和变态阶段增加。通过RNA干扰消除PLCG 1可以阻断20 E增强的化蛹，导致幼虫死亡和化蛹缺陷，并抑制20 E诱导的基因表达。20 E可诱导PLCG 1在胞质酪氨酸激酶（Src）同源2结构域的酪氨酸磷酸化，然后决定PLCG 1向质膜的迁移。G蛋白偶联受体（GPCR）抑制剂苏拉明，Src家族激酶抑制剂PP 2，以及蜕皮激素相关GPCR（ErGPCR）和G（q）的耗竭抑制20 E诱导的PLCG 1酪氨酸磷酸化。PLCG 1参与20 E诱导的Ca 2+内流。抑制GPCR、PLC、三磷酸肌醇受体和钙通道可抑制20 E诱导的Ca ~（2+）内流。通过钙信号传导，PLCG 1介导由蜕皮激素反应元件驱动的转录激活。通过PLCG 1和钙信号，20 E调节PKC磷酸化的USP 1在Ser-21，以确定其蜕皮激素反应元件结合活性。这些结果表明，20 E激活PLCG 1通过ErGPCR和Src家族激酶调节Ca 2+内流和PKC磷酸化的USP 1，随后调节基因转录变态。
Background: PLCG1 plays an important role in calcium signaling. Results: PLCG1 up-regulates 20E-induced calcium signaling and regulates USP1 PKC phosphorylation in the lepidopteran insect Helicoverpa armigera. Conclusion: 20E activates PLCG1 to induce calcium influx to regulate USP1 PKC phosphorylation for gene expression. Significance: Our study establishes a link between the nongenomic pathway and genomic pathway in steroid hormone 20E signaling.In addition to the classical nuclear receptor pathway, there is a nongenomic pathway in the cell membrane that regulates gene expression in animal steroid hormone signaling; however, this mechanism is unclear. Here, we report that the insect steroid hormone 20-hydroxyecdysone (20E) regulates calcium influx via phospholipase C1 (PLCG1) to modulate the protein kinase C phosphorylation of the transcription factor ultraspiracle (USP1) in the lepidopteran insect Helicoverpa armigera. The PLCG1 mRNA levels are increased during the molting and metamorphic stages. The depletion of PLCG1 by RNA interference can block 20E-enhanced pupation, cause larvae death and pupation defects, and repress 20E-induced gene expression. 20E may induce the tyrosine phosphorylation of PLCG1 at the cytosolic tyrosine kinase (Src) homology 2 domains and then determine the migration of PLCG1 toward the plasma membrane. The G-protein-coupled receptor (GPCR) inhibitor suramin, Src family kinase inhibitor PP2, and the depletions of ecdysone-responsible GPCR (ErGPCR) and G(q) restrain the 20E-induced tyrosine phosphorylation of PLCG1. PLCG1 participates in the 20E-induced Ca2+ influx. The inhibition of GPCR, PLC, inositol 1,4,5-trisphosphate receptor, and calcium channels represses the 20E-induced Ca2+ influx. Through calcium signaling, PLCG1 mediates the transcriptional activation driven by the ecdysone-response element. Through PLCG1 and calcium signaling, 20E regulates PKC phosphorylation of USP1 at Ser-21 to determine its ecdysone-response element binding activity. These results suggest that 20E activates PLCG1 via the ErGPCR and Src family kinases to regulate Ca2+ influx and PKC phosphorylation of USP1 to subsequently modulate gene transcription for metamorphosis.