Modulation of TOR complex 2 signaling by the stress-activated MAPK pathway in fission yeast

Abstract

Sin1 is a substrate-binding subunit of Target Of Rapamycin Complex 2 (TORC2), an evolutionarily conserved protein kinase complex. In fission yeast, Sin1 was also identified as a protein that interacts with Spc1/Sty1 stress-activated protein kinase (SAPK) and 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 Atf1 transcription factor, and the Gpd1 glycelrol-3-phosphate dehydrogenase, whose expression is induced upon osmostress by the Spc1-Atf1 pathway. Thus, cellular adaptation to osmostress seems to be 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.