Metabolic signaling : role and mechanism of a metabolic intermediate in glycolysis
| Project/Area Number |
17380201
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied molecular and cellular biology
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| Research Institution | Kyoto University |
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Principal Investigator |
INOUE Yoshiharu Kyoto University, Grd Sch. Of Agile, Associate Professor (70203263)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,380,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2007: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2006: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2005: ¥5,500,000 (Direct Cost: ¥5,500,000)
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| Keywords | Metabolic stress / Yeast / Signal transduction / Methylglyoxal / MAP kinase / Tyrosine phosphatase / PI3キナーゼ / メンブレントラフィック / メチルグリキオサール |
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| Research Abstract |
Methylglyoxal (MG) is a typical 2-oxoaldehyde derived from glycolysis, although it inhibits the growth of cells in all types of organism. Hence, it has been questioned why such a toxic metabolite is synthesized via the ubiquitous energy-generating pathway.
In this project, we found that MG activates the HOG-MAP kinase cascade in the budding yeast Saccharomyces cerevisiae. Two osmosensors, SIn1 and Sho1, have been identified to function upstream of the HOG-MAP kinase cascade, and we revealed that MG initiates the signal transduction to this MAP kinase cascade through the SIn1 branch.
To gain further insight into the role of MG as a signal initiator, next we analyzed the response of Schizosaccharomyces pombe to extracellular MG. Spc1, a stress-activated protein kinase (SAPK), was phosphorylated following the treatment with MG. No phosphorylation was observed in a wis1Δ mutant. The His-to-Asp phosphorelay system consisting of three histidine kinases (Phk1, Phk2 and Phk3), a phosphorelay protein (Spy1) and a response regulator (Mcs4) exists upstream of the Spc1-SAPK pathway. The phosphorylation of Spc1 following MG treatment was observed in phklΔphk2Δphk3Δ and spy1Δ cells, but not in mcs4Δ cells. These results suggest that S. pombe has alternative module(s) that direct the MG signal to the SAPK pathway via Mcs4. Additionally, we found that phosphorylation of Spc1 by treatment with MG in S. pombe cells defective in glyoxalase I, an enzyme crucial for the metabolism of MG, continues for a longer period than in wild-type cells. We revealed that MG inhibits the activity of the protein phosphatase responsible for the dephosphorylation of Spc1. Taken togeterh, we propose that MG functions as a signal initiator in yeast.
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] The glycolytic metabolite methylglyoxal activates Pap1 and Sty1 stress responses in Schizosaccharomyces pombe.2005
Author(s)
Zuin, A., Vivancos, A.P., Sanso, M., Takatsume, Y., Ayte, J., Inoue, Y., Hidalgo, E.
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Journal Title
J.Biol.Chem. 280(44)
Pages: 36708-36713
Related Report
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[Journal Article] Cytosolic proteins as principal copper buffer in an early response to copper by yeast cells.2005
Author(s)
Bi, W., Inai, Y., Shiraishi, N., Maeta, K., Takatsume, Y., Inoue, Y., Nishikimi, M.
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Journal Title
J.Clin.Biochem.Nutr. 36(1)
Pages: 19-27
NAID
Related Report
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