Methylglyoxal Activates the Target of Rapamycin Complex 2-Protein Kinase C Signaling Pathway in Saccharomyces cerevisiae

Abstract

© 2015, American Society for Microbiology. Methylglyoxal is a typical 2-oxoaldehyde derived from glycolysis. We show here that methylglyoxal activates the Pkc1-Mpk1 mitogen-activated protein (MAP) kinase cascade in a target of rapamycin complex 2 (TORC2)-dependent manner in the budding yeast Saccharomyces cerevisiae. We demonstrate that TORC2 phosphorylates Pkc1 at Thr 1125 and Ser 1143 . Methylglyoxal enhanced the phosphorylation of Pkc1 at Ser 1143 , which transmitted the signal to the downstream Mpk1 MAP kinase cascade. We found that the phosphorylation status of Pkc1T 1125 affected the phosphorylation of Pkc1 at Ser 1143 , in addition to its protein levels. Methylglyoxal activated mammalian TORC2 signaling, which, in turn, phosphorylated Akt at Ser 473 . Our results suggest that methylglyoxal is a conserved initiator of TORC2 signaling among eukaryotes.