Sequestration of the PKC ortholog Pck2 in stress granules as a feedback mechanism of MAPK signaling in fission yeast
Sequestration of the PKC ortholog Pck2 in stress granules as a feedback mechanism of MAPK signaling in fission yeast
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DOI：
10.1242/jcs.250191
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发表时间：
2021-01-01
影响因子：
4
通讯作者：
Sugiura, Reiko
中科院分区：
文献类型：
--
作者：
Kanda, Yuki;Satoh, Ryosuke;Sugiura, Reiko
蛋白激酶C（PKC）信号传导是高度保守的信号传导模块，其经由包括MAPK信号传导的各种信号传导途径在从细胞增殖到细胞死亡的无数生理过程中发挥中心作用。应激颗粒（SG）是在暴露于环境应激的细胞中聚集的非膜性胞质灶。本研究探讨了SGs在裂殖酵母PKC/MAPK信号通路激活中的作用。高温胁迫（HHS）诱导Pmk 1 MAPK活化和Pck 2从细胞尖端易位到多聚腺苷酸结合蛋白（Pabp）阳性的SG。pck 2分散从细胞尖端需要pck 2激酶活性，和组成型活性pck 2表现出增加易位到SG。重要的是，Pmk 1缺失损害了Pck 2向SG的募集，表明MAPK激活刺激Pck 2 SG易位。一致的是，HHS诱导的SGs延迟了Pck 2在细胞尖端的重新定位，从而阻断了从HHS恢复后随后的Pmk 1重新激活。HHS将Pck 2分配到含有Pabp阳性SG的部分中，这导致可溶性部分中Pck 2丰度和激酶活性降低。总之，这些结果表明，MAPK依赖性Pck 2 SG募集作为一种反馈机制，以拦截HHS诱导的PKC/MAPK激活，这可能是PKC相关疾病的基础。
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.