Division of Biological Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.
Okinawa Institute of Science and Technology Graduate University, Onna-son, Okinawa 904-0495, Japan.
J Cell Sci. 2019 Oct 10;132(19):jcs236133. doi: 10.1242/jcs.236133.
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.
Sin1 是雷帕霉素复合物 2（TORC2）的底物结合亚基，TORC2 是一种进化上保守的蛋白激酶复合物。在裂殖酵母中，Sin1 也被鉴定为与应激激活蛋白激酶（SAPK）途径中的 Spc1（也称为 Sty1）相互作用的蛋白质。因此，本研究检查了 TORC2 和 Spc1 信号之间的关系。我们发现 Spc1 的常见对接（CD）结构域与 Sin1 中的一簇碱性氨基酸残基相互作用。尽管在功能 Spc1 级联缺失的情况下 TORC2 活性降低表明 Spc1 对 TORC2 的正向调节，但这种调节似乎独立于 Sin1-Spcl 相互作用。高渗胁迫会短暂抑制 TORC2，其迅速恢复依赖于 Spc1、转录因子 Atf1 和甘油-3-磷酸脱氢酶 Gpd1，Spc1-Atf1 途径在 osmostress 下诱导它们的表达。因此，细胞对渗透压胁迫的适应对于 TORC2 的重新激活似乎很重要，尽管 Spc1 和 Atf1 也有助于在没有渗透压胁迫的情况下激活 TORC2。这些结果表明 SAPK 和 TORC2 途径的协调作用，这两者对于裂殖酵母细胞在环境胁迫下生存都是必不可少的。
