Atf1 is a target of the mitogen-activated protein kinase Pmk1 and regulates cell integrity in fission yeast
Atf1 is a target of the mitogen-activated protein kinase Pmk1 and regulates cell integrity in fission yeast
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DOI：
10.1091/mbc.e07-03-0282
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发表时间：
2007-12-01
影响因子：
3.3
通讯作者：
Sugiura, Reiko
中科院分区：
文献类型：
--
作者：
Takada, Hirofumi;Nishimura, Masayuki;Sugiura, Reiko
在裂殖酵母中，敲除钙调磷酸酶基因导致对Cl-的超敏反应，并且编码Pmk 1促分裂原活化蛋白激酶（MAPK）的双特异性磷酸酶的pmp 1（+）的过表达或敲除Pmk 1途径的组分补充了钙调磷酸酶缺失的Cl-超敏反应。在这里，我们发现，ptcl（+）和ptc 3（+）的过度表达，都编码2C型蛋白磷酸酶（PP 2C），以前已知的Wis 1 Spc 1Atf 1应激激活MAPK信号通路，抑制钙调磷酸酶缺失的Cl-超敏反应。我们还证明了这两个PP 2Cs和pyp 2（+）的mRNA水平，Spc 1的另一个负调节因子，依赖于Pmk 1。值得注意的是，Atf 1的缺失，而不是Spc 1的缺失，表现出对细胞壁损伤剂的超敏反应，并且还抑制了钙调磷酸酶缺失的Cl-超敏反应，这两者都是Pmk 1 MAPK通路的组分突变所共有的特征表型。此外，米卡芬净治疗诱导Pmk 1过度活化，导致Atf 1过度磷酸化。总之，我们的研究结果表明，PP 2C参与了Pmk 1信号的负反馈回路，结果还表明，Atf 1是Pmk 1 MAPK下游细胞完整性信号的关键组成部分。
In fission yeast, knockout of the calcineurin gene resulted in hypersensitivity to Cl-, and the overexpression of pmp1(+) encoding a dual-specificity phosphatase for Pmk1 mitogen-activated protein kinase (MAPK) or the knockout of the components of the Pmk1 pathway complemented the Cl- hypersensitivity of calcineurin deletion. Here, we showed that the overexpression of ptcl(+) and ptc3(+), both encoding type 2C protein phosphatase (PP2C), previously known to inactivate the Wis1Spc1Atf1 stress-activated MAPK signaling pathway, suppressed the Cl- hypersensitivity of calcineurin deletion. We also demonstrated that the mRNA levels of these two PP2Cs and pyp2(+), another negative regulator of Spc1, are dependent on Pmk1. Notably, the deletion of Atf1, but not that of Spc1, displayed hypersensitivity to the cell wall-damaging agents and also suppressed the Cl- hypersensitivity of calcineurin deletion, both of which are characteristic phenotypes shared by the mutation of the components of the Pmk1 MAPK pathway. Moreover, micafungin treatment induced Pmk1 hyperactivation that resulted in Atf1 hyperphosphorylation. Together, our results suggest that PP2C is involved in a negative feedback loop of the Pmk1 signaling, and results also demonstrate that Atf1 is a key component of the cell integrity signaling downstream of Pmk1 MAPK.