期刊
JOURNAL OF CELL SCIENCE
卷 135, 期 17, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.259988
关键词
TORC2; Phosphatidylserine; Phospholipase C; Yeast; Signaling
类别
资金
- Japan Society for the Promotion of Science (JSPS) KAKENHI Grants [19K05949, 20H03251, 21H02103, 21K19079]
- Lotte Foundation, Japan, Shigemitsu Prize
This study found that methylglyoxal (MG) activates the TORC2-Ypk1/2 and TORC2-Pkc1 signaling pathways, and that phosphatidylserine plays a role in their activation. The Rho family GTPase Cdc42 and phosphatidylinositol-specific phospholipase C, Plc1, were also found to contribute to the activation of these signaling pathways.
Target of rapamycin (TOR) forms two distinct complexes, TORC1 and TORC2, to exert its essential functions in 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 those for TORC1 signaling. In the budding yeast Saccharomyces cerevisiae, TORC2 targets the protein kinases Ypk1 and Ypk2 (hereafter Ypk1/2), and Pkc1 for phosphorylation. Plasma membrane stress is known to activate 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 TORC2Pkc1 signaling.
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