RRC ID 50374
Author Nomura W, Maeta K, Inoue Y.
Title Phosphatidylinositol 3,5-bisphosphate is involved in methylglyoxal-induced activation of the Mpk1 mitogen-activated protein kinase cascade in Saccharomyces cerevisiae.
Journal J Biol Chem
Abstract Methylglyoxal (MG) is a natural metabolite derived from glycolysis, and this 2-oxoaldehyde has been implicated in some diseases including diabetes. However, the physiological significance of MG for cellular functions is yet to be fully elucidated. We previously reported that MG activates the Mpk1 (MAPK) cascade in the yeast Saccharomyces cerevisiae To gain further insights into the cellular functions and responses to MG, we herein screened yeast-deletion mutant collections for susceptibility to MG. We found that mutants defective in the synthesis of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) are more susceptible to MG. PtdIns(3,5)P2 levels increased following MG treatment, and vacuolar morphology concomitantly changed to a single swollen shape. MG activated the Pkc1-Mpk1 MAPK cascade in which a small GTPase Rho1 plays a crucial role, and the MG-induced phosphorylation of Mpk1 was impaired in mutants defective in the PtdIns(3,5)P2 biosynthetic pathway. Of note, heat shock-induced stress also provoked Mpk1 phosphorylation in a Rho1-dependent manner; however, PtdIns(3,5)P2 was dispensable for the heat shock-stimulated activation of this signaling pathway. Our results suggest that PtdIns(3,5)P2 is specifically involved in the MG-induced activation of the Mpk1 MAPK cascade and in the cellular adaptation to MG-induced stress.
Volume 292(36)
Pages 15039-15048
Published 2017-9-8
DOI 10.1074/jbc.M117.791590
PII S0021-9258(20)34323-4
PMID 28743744
PMC PMC5592679
MeSH Enzyme Activation / drug effects Mitogen-Activated Protein Kinases / metabolism* Phosphatidylinositol Phosphates / metabolism* Pyruvaldehyde / metabolism Pyruvaldehyde / pharmacology* Saccharomyces cerevisiae / drug effects* Saccharomyces cerevisiae / enzymology* Signal Transduction / drug effects
IF 4.238
Times Cited 3
Yeast BY21465(YPH250) BY23849(BY4741) BY3896(SEY6210) BYP1419