LAUSR

The target of rapamycin (TOR) forms two distinct complexes, TORC1 and TORC2, to exert its functions essential for cellular growth and homeostasis. TORC1 signaling is regulated in response to nutrients such as amino acids and glucose; however, the mechanisms underlying the activation of TORC2 signaling are still poorly understood compared to TORC1 signaling. In the budding yeast Saccharomyces cerevisiae, TORC2 targets protein kinases Ypk1, Ypk2, and Pkc1 for phosphorylation. Plasma membrane stress is known to activate the TORC2-Ypk1/2 signaling. We have previously reported that methylglyoxal (MG), a metabolite derived from glycolysis, activates TORC2-Pkc1 signaling. In this study, we found that MG activates the TORC2-Ypk1/2 and TORC2-Pkc1 signaling, and that phosphatidylserine is involved in the activation of both signaling pathways. We also demonstrated that the Rho-family GTPase Cdc42 contributes to the plasma membrane stress-induced activation of TORC2-Ypk1/2 signaling. Furthermore, we revealed that phosphatidylinositol-specific phospholipase C, Plc1, contributes to the activation of both TORC2-Ypk1/2 and TORC2-Pkc1 signaling.