Heat stress activates fission yeast Spc1/StyI MAPK by a MEKK-independent mechanism
Heat stress activates fission yeast Spc1/StyI MAPK by a MEKK-independent mechanism
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DOI：
10.1091/mbc.9.6.1339
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发表时间：
1998-06-01
影响因子：
3.3
通讯作者：
Russell, P
中科院分区：
文献类型：
--
作者：
Shiozaki, K;Shiozaki, M;Russell, P
裂变酵母Spc 1/StyI MAPK被许多环境损伤激活，包括高渗透压，氧化应激和热休克。Spc 1/StyI由Wis 1激活，Wis 1是一种MAPK激酶（MEK），Wis 1本身由Wik 1/Wak 1/Wis 4激活，Wis 4是一种MEK激酶（MEKK）。Spc 1/StyI被酪氨酸磷酸酶Pyp 1和Pyp 2灭活。Pyp 1的抑制最近被报道在氧化应激和热休克反应中起着至关重要的作用。这些结论基于三个发现：1）渗透、氧化和热应激激活Wis 4细胞中的Spc 1/StyI; 2）氧化应激和热休克激活表达Wis 1AA的细胞中的Spc 1/StyI，其中MEKK共有磷酸化位点被丙氨酸取代; 3）Spc 1/StyI在Delta pyp 1细胞中被最大程度地激活。与这些发现相反，我们报告：1）Spc 1/StyI激活渗透压大大减少在wis 4细胞; 2）wis 1-AA和Delta wis 1细胞具有相同的表型;和3）所有形式的应力激活Spc 1/StyI在Delta pyp 1细胞。我们还报告说，热休克，而不是渗透或氧化应激，激活Spc 1在WIS 1-DD细胞，表达WIS 1蛋白，MEKK共识磷酸化位点替换为天冬氨酸。因此，渗透压和氧化应激激活Spc 1/StyI的MEKK依赖的过程，而热休克激活Spc 1/StyI的一种新的机制，不需要MEKK激活或Pyp 1抑制。
Fission yeast Spc1/StyI MAPK is activated by many environmental insults including high osmolarity, oxidative stress, and heat shock. Spc1/StyI is activated by Wis1, a MAPK kinase (MEK), which is itself activated by Wik1/Wak1/Wis4, a MEK kinase (MEKK). Spc1/StyI is inactivated by the tyrosine phosphatases Pyp1 and Pyp2. Inhibition of Pyp1 was recently reported to play a crucial role in the oxidative stress and heat shock responses. These conclusions were based on three findings: 1) osmotic, oxidative, and heat stresses activate Spc1/StyI in wis4 cells; 2) oxidative stress and heat shock activate Spc1/StyI in cells that express Wis1AA, in which MEKK consensus phosphorylation sites were replaced with alanine; and 3) Spc1/StyI is maximally activated in Delta pyp1 cells. Contrary to these findings, we report: 1) Spc1/StyI activation by osmotic stress is greatly reduced in wis4 cells; 2) wis1-AA and Delta wis1 cells have identical phenotypes; and 3) all forms of stress activate Spc1/StyI in Delta pyp1 cells. We also report that heat shock, but not osmotic or oxidative stress, activate Spc1 in wis1-DD cells, which express Wis1 protein that has the MEKK consensus phosphorylation sites replaced with aspartic acid. Thus osmotic and oxidative stress activate Spc1/StyI by a MEKK-dependent process, whereas heat shock activates Spc1/StyI by a novel mechanism that does not require MEKK activation or Pyp1 inhibition.