Activation of BNGR-A24 by Direct Interaction with Tachykinin-Related Peptides from the Silkworm Bombyx mori Leads to the Gq- and Gs-Coupled Signaling Cascades
Activation of BNGR-A24 by Direct Interaction with Tachykinin-Related Peptides from the Silkworm Bombyx mori Leads to the Gq- and Gs-Coupled Signaling Cascades
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DOI：
10.1021/bi5007207
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发表时间：
2014-10-28
期刊：
影响因子：
2.9
通讯作者：
Zhou, Naiming
中科院分区：
文献类型：
--
作者：
He, Xiaobai;Zang, Jiashu;Zhou, Naiming
速激肽是动物界最大的肽家族之一，通过G蛋白偶联受体（GPCR）发挥其多种作用。在这项研究中，TKRP被鉴定为BNGR-A24的特异性内源性配体，因此将BNGR-A24命名为BmTKRPR。使用哺乳动物细胞系HEK 293和昆虫细胞系Sf 21，进一步表征表明BmTKRPR被激活，从而导致cAMP的细胞内积累、Ca 2+动员和ERK 1/2磷酸化以G（s）和G（q）底物敏感的方式进行。此外，定量逆转录聚合酶链反应分析和dsRNA介导的敲除实验表明，BmTKRPR在调节摄食和生长中可能发挥作用。我们的研究结果增强了对TKRP系统在调节基本生理过程中的理解。
Tachykinins constitute one of the largest peptide families in the animal kingdom and exert their diverse actions via G protein-coupled receptors (GPCRs). In this study, the Bombyx tachykinin-related peptides (TKRPs) were identified as specific endogenous ligands for the Bombyx neuropeptide GPCR A24 (BNGR-A24) and thus designated BNGR-A24 as BmTKRPR. Using both mammalian cell line HEK293 and insect cell line Sf21, further characterization demonstrated that BmTKRPR was activated, thus resulting in intracellular accumulation of cAMP, Ca2+ mobilization, and ERK1/2 phosphorylation in a G(s) and G(q) inhibitor-sensitive manner. Moreover, quantitative reverse transcriptase polymerase chain reaction analysis and dsRNA-mediated knockdown experiments suggested a possible role for BmTKRPR in the regulation of feeding and growth. Our findings enhance the understanding of the Bombyx TKRP system in the regulation of fundamental physiological processes.