G 蛋白偶联受体激酶 2 终止类固醇激素 20-羟蜕皮激素信号转导中的 G 蛋白偶联受体功能。
G-protein-coupled receptor kinase 2 terminates G-protein-coupled receptor function in steroid hormone 20-hydroxyecdysone signaling.
机构信息
Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China.
出版信息
Sci Rep. 2016 Jul 14;6:29205. doi: 10.1038/srep29205.
G-protein-coupled receptors (GPCRs) transmit extracellular signals across the cell membrane. GPCR kinases (GRKs) desensitize GPCR signals in the cell membrane. However, the role and mechanism of GRKs in the desensitization of steroid hormone signaling are unclear. In this study, we propose that GRK2 is phosphorylated by protein kinase C (PKC) in response to induction by the steroid hormone 20-hydroxyecdysone (20E), which determines its translocation to the cell membrane of the lepidopteran Helicoverpa armigera. GRK2 protein expression is increased during the metamorphic stage because of induction by 20E. Knockdown of GRK2 in larvae causes accelerated pupation, an increase in 20E-response gene expression, and advanced apoptosis and metamorphosis. 20E induces translocation of GRK2 from the cytoplasm to the cell membrane via steroid hormone ecdysone-responsive GPCR (ErGPCR-2). GRK2 is phosphorylated by PKC on serine 680 after induction by 20E, which leads to the translocation of GRK2 to the cell membrane. GRK2 interacts with ErGPCR-2. These data indicate that GRK2 terminates the ErGPCR-2 function in 20E signaling in the cell membrane by a negative feedback mechanism.
G 蛋白偶联受体（GPCRs）将细胞外信号传递穿过细胞膜。G 蛋白偶联受体激酶（GRKs）使 GPCR 信号在细胞膜中脱敏。然而，GRKs 在甾体激素信号脱敏中的作用和机制尚不清楚。在这项研究中，我们提出 GRK2 可被蛋白激酶 C（PKC）磷酸化，以响应甾体激素 20-羟基蜕皮甾酮（20E）的诱导，这决定了其向鳞翅目昆虫棉铃虫的细胞膜的易位。由于 20E 的诱导，GRK2 蛋白在变态阶段的表达增加。幼虫中 GRK2 的敲低导致化蛹加速、20E-反应基因表达增加以及提前凋亡和变态。20E 通过甾体激素蜕皮激素反应 GPCR（ErGPCR-2）诱导 GRK2 从细胞质向细胞膜易位。GRK2 在被 20E 诱导后在丝氨酸 680 被 PKC 磷酸化，导致 GRK2 向细胞膜的易位。GRK2 与 ErGPCR-2 相互作用。这些数据表明，GRK2 通过负反馈机制终止细胞膜中 ErGPCR-2 在 20E 信号转导中的功能。
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