Protein kinase C (PKC) signaling is a highly conserved signaling module that plays a central role in a myriad of physiological processes, ranging from cell proliferation to cell death, via various signaling pathways, including MAPK signaling. Stress granules (SGs) are non-membranous cytoplasmic foci that aggregate in cells exposed to environmental stresses. Here, we explored the role of SGs in PKC/MAPK signaling activation in fission yeast. High-heat stress (HHS) induced Pmk1 MAPK activation and Pck2 translocation from the cell tips into poly(A)-binding protein (Pabp)-positive SGs. Pck2 dispersal from the cell tips required Pck2 kinase activity, and constitutively active Pck2 exhibited increased translocation to SGs. Importantly, Pmk1 deletion impaired Pck2 recruitment to SGs, indicating that MAPK activation stimulates Pck2 SG translocation. Consistently, HHS-induced SGs delayed Pck2 relocalization at the cell tips, thereby blocking subsequent Pmk1 reactivation after recovery from HHS. HHS partitioned Pck2 into the Pabp-positive SG-containing fraction, which resulted in reduced Pck2 abundance and kinase activity in the soluble fraction. Taken together, these results indicate that MAPK-dependent Pck2 SG recruitment serves as a feedback mechanism to intercept PKC/MAPK activation induced by HHS, which might underlie PKC-related diseases.

蛋白激酶 C (PKC) 信号传导是一种高度保守的信号传导模块，通过各种信号传导途径（包括 MAPK 信号传导）在无数生理过程中发挥核心作用，从细胞增殖到细胞死亡。应力颗粒 (SGs) 是非膜细胞质病灶，在暴露于环境压力的细胞中聚集。在这里，我们探讨了 SGs 在裂变酵母中 PKC/MAPK 信号激活中的作用。高热应激 (HHS) 诱导 Pmk1 MAPK 激活和 Pck2 从细胞尖端易位到聚 (A) 结合蛋白 (Pabp) 阳性 SGs。Pck2 从细胞尖端的扩散需要 Pck2 激酶活性，并且组成型活跃的 Pck2 表现出向 SGs 的易位增加。重要的是，Pmk1 缺失损害了 Pck2 向 SG 的募集，表明 MAPK 激活刺激 Pck2 SG 易位。一致地，HHS 诱导的 SGs 延迟了 Pck2 在细胞尖端的重新定位，从而阻止了从 HHS 恢复后随后的 Pmk1 重新激活。HHS 将 Pck2 划分为含有 Pabp 阳性 SG 的部分，这导致可溶部分中 Pck2 丰度和激酶活性降低。综上所述，这些结果表明 MAPK 依赖的 Pck2 SG 募集作为一种反馈机制来拦截 HHS 诱导的 PKC/MAPK 激活，这可能是 PKC 相关疾病的基础。