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. We demonstrate that TORC2 phosphorylates Pkc1 at Thr¹¹²⁵ and Ser¹¹⁴³. Methylglyoxal enhanced the phosphorylation of Pkc1 at Ser¹¹⁴³, which transmitted the signal to the downstream Mpk1 MAP kinase cascade. We found that the phosphorylation status of Pkc1^T1125 affected the phosphorylation of Pkc1 at Ser¹¹⁴³, in addition to its protein levels. Methylglyoxal activated mammalian TORC2 signaling, which, in turn, phosphorylated Akt at Ser⁴⁷³. Our results suggest that methylglyoxal is a conserved initiator of TORC2 signaling among eukaryotes.

Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.01118-14.

ACKNOWLEDGMENTS

We thank T. Kawada, N. Takahashi, T. Goto, Y. Kim, S. Izawa, and K. Maeta for their technical support and helpful discussions. We are grateful to M. N. Hall, D. E. Levin, T. Miyakawa, J. Thorner, Y. Ohya, J. J. Heinisch, M. Y. Chen, M. S. Cyert, J. R. Broach, K. Irie, and the National Bio-Resource Project (NBRP) of MEXT, Japan, for providing the plasmids and yeast strains.