Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.
Elife. 2024 Aug 13;13:RP93877. doi: 10.7554/eLife.93877.
Apicomplexan parasites balance proliferation, persistence, and spread in their metazoan hosts. AGC kinases, such as PKG, PKA, and the PDK1 ortholog SPARK, integrate environmental signals to toggle parasites between replicative and motile life stages. Recent studies have cataloged pathways downstream of apicomplexan PKG and PKA; however, less is known about the global integration of AGC kinase signaling cascades. Here, conditional genetics coupled to unbiased proteomics demonstrates that SPARK complexes with an elongin-like protein to regulate the stability of PKA and PKG in the model apicomplexan . Defects attributed to SPARK depletion develop after PKG and PKA are down-regulated. Parasites lacking SPARK differentiate into the chronic form of infection, which may arise from reduced activity of a coccidian-specific PKA ortholog. This work delineates the signaling topology of AGC kinases that together control transitions within the asexual cycle of this important family of parasites.
顶复门寄生虫在其后生动物宿主中平衡增殖、持续存在和传播。AGC 激酶（如 PKG、PKA 和 PDK1 同源物 SPARK）整合环境信号，使寄生虫在复制和运动生命阶段之间转换。最近的研究已经对顶复门 PKG 和 PKA 的下游途径进行了编目；然而，关于 AGC 激酶信号级联的全局整合知之甚少。在这里，条件遗传学与无偏蛋白质组学相结合，证明 SPARK 与一个 elongin 样蛋白复合物，以调节模型顶复门中的 PKA 和 PKG 的稳定性。归因于 SPARK 耗尽的缺陷在 PKG 和 PKA 下调后出现。缺乏 SPARK 的寄生虫分化为慢性感染形式，这可能是由于一种 coccidian 特异性 PKA 同源物活性降低所致。这项工作描绘了 AGC 激酶的信号拓扑结构，这些激酶共同控制着这个重要的寄生虫家族的无性周期内的转变。
