The sleeping sickness parasite, Trypanosoma brucei, uses quorum sensing (QS) to balance proliferation and transmission potential in the mammal bloodstream. A signal transduction cascade regulates this process, a component of which is a divergent member of the DYRK family of protein kinases, TbDYRK. Phylogenetic and mutational analysis in combination with activity and phenotypic assays revealed that TbDYRK exhibits a pre-activated confirmation and an atypical HxY activation loop motif, unlike DYRK kinases in other eukaryotes. Phosphoproteomic comparison of TbDYRK null mutants with wild type parasites identified molecules that operate on both the inhibitory 'slender retainer' and activatory 'stumpy inducer' arms of the QS control pathway. One of these molecules, the RNA-regulator TbZC3H20, regulates parasite QS, this being dependent on the integrity of its TbDYRK phosphorylation site. This analysis reveals fundamental differences to conventional DYRK family regulation and links trypanosome environmental sensing, signal transduction and developmental gene expression in a coherent pathway.

中文翻译：

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非典型DYRK激酶将布鲁氏锥虫的群体感应与转录后基因调控联系起来

昏睡病寄生虫，布鲁氏锥虫，使用群体感应（QS）来平衡哺乳动物血流中的增殖和传播潜能。信号转导级联调节该过程，其组成是蛋白激酶DYRK家族TbDYRK的不同成员。系统发育和突变分析与活性和表型分析相结合显示，与其他真核生物中的DYRK激酶不同，TbDYRK具有预先激活的确认和非典型的HxY激活环基序。TbDYRK null突变体与野生型寄生虫的磷酸蛋白质组学比较鉴定了在QS控制途径的抑制性“细长固位体”和激活性“ s肿诱导子”臂上均起作用的分子。其中一种分子RNA调节剂TbZC3H20调节寄生虫QS，这取决于其TbDYRK磷酸化位点的完整性。该分析揭示了与常规DYRK家族调控的根本差异，并以一致的途径将锥虫环境感测，信号转导和发育基因表达联系起来。