Methylglyoxal as a Signal Initiator for Activation of the Stress-activated Protein Kinase Cascade in the Fission Yeast Schizosaccharomyces pombe*
Methylglyoxal as a Signal Initiator for Activation of the Stress-activated Protein Kinase Cascade in the Fission Yeast Schizosaccharomyces pombe*
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DOI：
10.1074/jbc.m511037200
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发表时间：
2006-04
影响因子：
4.8
通讯作者：
Yoshifumi Takatsume;S. Izawa;Y. Inoue
中科院分区：
文献类型：
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作者：
Yoshifumi Takatsume;S. Izawa;Y. Inoue
丙酮醛（MG）是一种典型的糖酵解产物。我们最近发现，MG激活转录因子，如Yap 1和Msn 2，并触发Hog 1有丝分裂原激活的蛋白激酶级联在酿酒酵母。关于MG对Hog 1的激活，我们发现Sln 1，一种具有组氨酸激酶活性的Hog 1传感器，作为MG的传感器起作用（Maeta，K.，Izawa，S.，和Inoue，Y.（2005）J.Biol.Chem.280，253-260）。为了进一步了解MG作为信号启动子的作用，在这里，我们分析了裂殖酵母菌胞外MG的反应。应激激活蛋白激酶（SAPK）Spc 1在MG处理后磷酸化。在wis 1 Δ突变体中未观察到磷酸化。由三种组氨酸激酶（Phk 1、Phk 2和Phk 3）、磷酸化中继蛋白（Spy 1）和反应调节剂（Mcs 4）组成的His-to-Asp磷酸化中继系统存在于Spc 1-SAPK途径的上游。MG处理后，在phk 1 Δ phk 2 Δ phk 3 Δ和spy 1 Δ细胞中观察到Spc 1磷酸化，而在mcs 4 Δ细胞中未观察到。这些结果表明S.粟酒裂殖酵母具有通过Mcs 4将MG信号引导至SAPK途径的替代模块。此外，我们发现，转录因子Pap 1集中在细胞核中的MG响应，独立的Spc 1-SAPK途径。
Methylglyoxal (MG) is a typical 2-oxoaldehyde derived from glycolysis. We have recently found that MG activates transcription factors such as Yap1 and Msn2, and triggers a Hog1 mitogen-activated protein kinase cascade in Saccharomyces cerevisiae. Regarding the activation of Hog1 by MG, we found that Sln1, an osmosensor possessing histidine kinase activity, functions as a sensor of MG (Maeta, K., Izawa, S., and Inoue, Y. (2005) J. Biol. Chem. 280, 253–260). To gain further insight into the role of MG as a signal initiator, here we analyze 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 phk1Δphk2Δphk3Δ and spy1Δ cells, but not in mcs4Δ cells. These results suggest that S. pombe has an alternative module(s) that directs the MG signal to the SAPK pathway via Mcs4. Additionally, we found that the transcription factor Pap1 is concentrated in the nucleus in response to MG, independent of the Spc1-SAPK pathway.