Stress granules as a feedback mechanism of MAPK signaling by sequestering PKC/Pck2
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- Yuki Kanda
- Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kindai University, Japan
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- Ryosuke Satoh
- Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kindai University, Japan
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- Teruaki Takasaki
- Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kindai University, Japan
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- Naofumi Tomimoto
- Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kindai University, Japan
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- Kiko Tsuchiya
- Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kindai University, Japan
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- Chun An Tsai
- Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kindai University, Japan
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- Taemi Tanaka
- Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kindai University, Japan
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- Shu Kyomoto
- Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kindai University, Japan
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- Kozo Hamada
- Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kindai University, Japan
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- Toshinobu Fujiwara
- Laboratory of Biochemistry, Department of Pharmacy, Faculty of Pharmacy, Kindai University, Japan
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- Reiko Sugiura
- Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kindai University, Japan
説明
<jats:p>The PKC signaling is a highly conserved signaling module, which plays a central role in a myriad of physiological processes, ranging from cell proliferation to cell death via various signaling pathways, including MAPK. 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/PKC translocation from the cell tips into poly(A)-binding protein (Pabp)-positive SGs. Pck2 dispersal from the cell tips required Pck2 kinase activity and the constitutively active Pck2 promotes its translocation to SGs. Importantly, Pmk1 deletion impaired Pck2 recruitment into 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 the reduced Pck2 abundance and kinase activity in the soluble fraction. Collectively, MAPK-dependent Pck2 SG recruitment serves as a feedback mechanism to intercept PKC/MAPK activation induced by HHS, which might underlie PKC-related diseases.</jats:p>
収録刊行物
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- Journal of Cell Science
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Journal of Cell Science 134 jcs250191-, 2020-01-01
The Company of Biologists