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

Abstract

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.

Phosphorylation of lipid metabolic enzymes by yeast protein kinase C requires phosphatidylserine and diacylglycerol

“…We acknowledge that this finding alone does not generalize the PS dependency of Pkc1 activity on the protein targets in vivo. Yet, it is known that the C1 lipidbinding domain of Pkc1 is needed for the stress-mediated activation of the MAP kinase pathway (68), and that a role for PS is supported by the attenuation of the pathway in cho1 mutant cells (62).…”

TOR Signaling in Budding Yeast

“…On the other hand, methylglyoxal, a typical 2-oxoaldehyde derived from glycolysis [100], also activates the Pkc1-Mpk1 MAPK cascade; however, the methylglyoxal-induced activation of this pathway is not dependent on Wsc1/Mid2, whereas Rho1 is indispensable [101]. Besides Ypk1 and Ypk2, Pkc1 has also been identified as a direct substrate of TORC2 in S. cerevisiae, that is, Thr 1125 within the turn motif and Ser 1143 within the hydrophobic motif in Pkc1 are phosphorylated by TORC2 [101]. Methylglyoxal enhanced the phosphorylation levels of Pkc1 at Ser 1143 in a TORC2-dependent manner [101] (Figure 3).…”

“…A recent study reported that phosphatidylserine, one of the major glycerophospholipids prevailing in the plasma membrane, mediates the physical interaction between Pkc1 and Rho1 GTP [98,99]. On the other hand, methylglyoxal, a typical 2-oxoaldehyde derived from glycolysis [100], also activates the Pkc1-Mpk1 MAPK cascade; however, the methylglyoxal-induced activation of this pathway is not dependent on Wsc1/Mid2, whereas Rho1 is indispensable [101]. Besides Ypk1 and Ypk2, Pkc1 has also been identified as a direct substrate of TORC2 in S. cerevisiae, that is, Thr 1125 within the turn motif and Ser 1143 within the hydrophobic motif in Pkc1 are phosphorylated by TORC2 [101].…”

“…The methylglyoxal-induced activation of TORC2 is conserved in mammalian cells, that is, the phosphorylation levels of Ser 473 within the hydrophobic motif in Akt, a substrate of mTORC2, were enhanced following the treatment of mouse 3 T3-L1 cells with methylglyoxal [101].…”

“…Besides Ypk1 and Ypk2, Pkc1 has also been identified as a direct substrate of TORC2 in S. cerevisiae, that is, Thr 1125 within the turn motif and Ser 1143 within the hydrophobic motif in Pkc1 are phosphorylated by TORC2 [101]. Methylglyoxal enhanced the phosphorylation levels of Pkc1 at Ser 1143 in a TORC2-dependent manner [101] (Figure 3). …”