Glycolytic enzyme GAPDH promotes peroxide stress signaling through multistep phosphorelay to a MAPK cascade
Glycolytic enzyme GAPDH promotes peroxide stress signaling through multistep phosphorelay to a MAPK cascade
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DOI：
10.1016/j.molcel.2008.01.017
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发表时间：
2008-04-11
期刊：
影响因子：
16
通讯作者：
Shiozaki, Kazuhiro
中科院分区：
文献类型：
--
作者：
Morigasaki, Susumu;Shimada, Koichi;Shiozaki, Kazuhiro
通过双组分系统的环境刺激的磷酸化传递信号在细菌中是普遍的，并且也被真菌和植物利用。在裂殖酵母裂殖酵母中，过氧化物应激信号从Mak 2/3传感器激酶传递到Mpr 1含组氨酸的磷酸转移（HPt）蛋白，最后传递到Mcs 4反应调节剂，该调节剂激活MAP激酶级联。在这里，我们表明，出乎意料的是，糖酵解酶甘油醛-3-磷酸脱氢酶（GAPDH）物理关联的Mcs 4反应调节剂和应激反应的MAP激酶（MAPKKKs）。在H2 O2胁迫下，Tdh 1 GAPDH的Cys-152被瞬时氧化，这增强了Tdh 1与Mcs 4的结合。此外，Tdh 1对于Mprl HPt蛋白和Mcs 4反应调节剂之间的相互作用是必需的，因此对于磷酸化信号传导是必需的。这些结果表明，糖酵解酶GAPDH在磷酸化信号传导中起着重要作用，其中其氧化还原敏感的半胱氨酸残基可以提供额外的输入信号。
Phosphorelay signaling of environmental stimuli by two-component systems is prevailing in bacteria and also utilized by fungi and plants. In the fission yeast Schizosaccharomyces pombe, peroxide stress signals are transmitted, from the Mak2/3 sensor kinases to the Mpr1 histidine-containing phosphotransfer(HPt) protein and finally to the Mcs4 response regulator, which activates a MAP kinase cascade. Here we show that, unexpectedly, the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) physically associates with the Mcs4 response regulator and stress-responsive MAP kinase kinase kinases (MAPKKKs). In response to H2O2 stress, Cys-152 of the Tdh1 GAPDH is transiently oxidized, which enhances the association of Tdh1 with Mcs4. Furthermore, Tdh1 is essential for the interaction between the Mprl HPt protein and the Mcs4 response regulator and thus for phosphorelay signaling. These results demonstrate that the glycolytic enzyme GAPDH plays an essential role in the phosphorelay signaling, where its redox-sensitive cysteine residue may provide additional input signals.