Methoprene-tolerant 1 (Met1) is a basic-helix-loop-helix Per/Arnt/Sim (bHLH-PAS) protein identified as the intracellular receptor of juvenile hormone (JH). JH induces phosphorylation of Met1; however, the phosphorylation site and outcomes of phosphorylation are not well characterized. In the present study, using the lepidopteran insect and serious agricultural pest Helicoverpa armigera (cotton bollworm) as a model, we showed that JH III induced threonine-phosphorylation of Met1 at threonine 393 (Thr393) in the Per-Arnt-Sim (PAS) B domain. Thr393-phosphorylation was necessary for Met1 binding to the JH response element (JHRE) to promote the transcription of Kr-h1 (encoding transcription factor Krüppel homolog 1) because Thr393-phosphorylated Met1 increased its interaction with Taiman (Tai) and prevented the Met1-Met1 association. However, JH III could not prevent Met1-Met1 association after Met1-Thr393 was mutated, suggesting that Thr393-phosphorylation is an essential mechanism by which JH prevents Met1-Met1 association. The results showed that JH induces Met1 phosphorylation on Thr393, which prevents Met1-Met1 association, enhances Met1 interaction with Tai, and promotes the binding of Met1-Tai transcription complex to the E-box in the JHRE to regulate Kr-h1 transcription.

耐甲氧戊二烯 1 (Met1) 是一种碱性-螺旋-环-螺旋 Per/Arnt/Sim (bHLH-PAS) 蛋白，被鉴定为保幼激素 (JH) 的细胞内受体。JH 诱导 Met1 磷酸化；然而，磷酸化位点和磷酸化的结果并没有得到很好的表征。在本研究中，以鳞翅目昆虫和严重农业害虫棉铃虫（棉铃虫）为模型，我们表明 JH III 在 Per-Arnt-Sim (PAS) 中的苏氨酸 393 (Thr393) 处诱导了 Met1 的苏氨酸磷酸化B域。Thr393 磷酸化是 Met1 与 JH 反应元件 (JHRE) 结合以促进Kr-h1转录所必需的（编码转录因子 Krüppel 同源物 1），因为 Thr393 磷酸化的 Met1 增加了它与 Taiman (Tai) 的相互作用并阻止了 Met1-Met1 关联。然而，在 Met1-Thr393 突变后 JH III 不能阻止 Met1-Met1 结合，表明 Thr393 磷酸化是 JH 阻止 Met1-Met1 结合的基本机制。结果表明，JH 诱导 Thr393 上的 Met1 磷酸化，阻止 Met1-Met1 结合，增强 Met1 与 Tai 的相互作用，并促进 Met1-Tai 转录复合物与 JHRE 中的 E-box 结合以调节Kr-h1转录。