Modulation of TOR complex 2 signaling by the stress-activated MAPK pathway in fission yeast
Modulation of TOR complex 2 signaling by the stress-activated MAPK pathway in fission yeast
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DOI：
10.1242/jcs.236133
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发表时间：
2019-10-01
影响因子：
4
通讯作者：
Shiozaki, Kazuhiro
中科院分区：
文献类型：
--
作者：
Morigasaki, Susumu;Chin, Lit Chein;Shiozaki, Kazuhiro
Sin1是雷帕霉素复合物2 （TORC2）靶标的底物结合亚基，是一种进化上保守的蛋白激酶复合物。在裂变酵母中，Sin1也被鉴定为在应激激活蛋白激酶（SAPK）途径中与Spc1（也称为Sty1）相互作用的蛋白质。因此，本研究考察了TORC2和Spc1信号传导之间的关系。我们发现Spc1的公共对接（CD）结构域与Sin1中的一簇碱性氨基酸残基相互作用。虽然在没有功能性Spc1级联的情况下，TORC2活性降低表明Spc1对TORC2有正向调节作用，但这种调节似乎与Sin1-Spc1相互作用无关。高渗胁迫可短暂抑制TORC2，其快速恢复依赖于Spc1、转录因子Atf1和甘油-3-磷酸脱氢酶Gpd1，其在渗透胁迫下通过Spc1-Atf1通路诱导表达。因此，细胞对渗透胁迫的适应似乎对TORC2的再激活很重要，尽管Spc1和Atf1在没有渗透胁迫的情况下也有助于TORC2的激活。这些结果表明SAPK和TORC2通路的协同作用，两者都是裂变酵母细胞在环境胁迫下生存所必需的。
Sin1 is a substrate-binding subunit of target of rapamycin complex 2 (TORC2), an evolutionarily conserved protein kinase complex. In fission yeast, Sin1 has also been identified as a protein that interacts with Spc1 (also known as Sty1) in the stress-activated protein kinase (SAPK) pathway. Therefore, this study examined the relationship between TORC2 and Spc1 signaling. We found that the common docking (CD) domain of Spc1 interacts with a cluster of basic amino acid residues in Sin1. Although diminished TORC2 activity in the absence of the functional Spc1 cascade suggests positive regulation of TORC2 by Spc1, such regulation appears to be independent of the Sin1-Spc1 interaction. Hyperosmotic stress transiently inhibits TORC2, and its swift recovery is dependent on Spc1, the transcription factor Atf1, and the glycelrol-3-phosphate dehydrogenase Gpd1, whose expression is induced upon osmostress by the Spc1-Atf1 pathway. Thus, cellular adaptation to osmostress seems important for TORC2 reactivation, though Spc1 and Atf1 contribute to TORC2 activation also in the absence of osmostress. These results indicate coordinated actions of the SAPK and TORC2 pathways, both of which are essential for fission yeast cells to survive environmental stress.