Protein phosphatase 2C acts independently of stress-activated kinase cascade to regulate the stress response in fission yeast
Protein phosphatase 2C acts independently of stress-activated kinase cascade to regulate the stress response in fission yeast
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DOI：
10.1074/jbc.272.28.17873
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发表时间：
1997-07-11
影响因子：
4.8
通讯作者：
Russell, P
中科院分区：
文献类型：
--
作者：
Gaits, F;Shiozaki, K;Russell, P
应激激活的信号转导通路在多种真核生物中广泛保守，在多种形式的逆境中起着至关重要的作用。因此，重要的是要发现这些途径是如何同时受到积极和消极调控的。最近的遗传学研究表明，蛋白磷酸酶2C(PP2C)是一种新的应激反应途径的负调节因子，在萌芽酵母和分裂酵母中都是如此，而且，假设PP2C去磷酸化了处于应激激活信号转导途径核心的蛋白激酶级联的一个或多个成分，在这里，我们对裂解酵母裂殖酵母进行了遗传学和生化研究，证明了这一假说是错误的，并表明PP2C相反地负调节该途径的下游成分。首先，PPSC的高表达产生的表型与Wik1-Wis1-SPc1应激激活激酶级联的负调控不一致。第二，PPSC的高表达导致SPc1持续激活酪氨酸磷酸化。第三，依赖于SPc1的转录因子底物atf1的磷酸化不受PP2C高表达的影响，第四，PP2C的高表达抑制了一个依赖于atf1的应激反应基因的转录，这些研究强烈地表明，PP2C在应激激活的信号转导途径中作用于SPc1激酶的下游。
Stress-activated signal transduction pathways, which are largely conserved among a broad spectrum of eukaryotic species, have a crucial role in the survival of many forms of stress. It is therefore important to discover how these pathways are both positively and negatively regulated. Recent genetic studies have implicated protein phosphatase 2C (PP2C) as a novel negative regulator of stress response pathways in both budding and fission yeasts, Moreover, it was hypothesized that PP2C dephosphorylates one or more components of protein kinase cascades that are at the core of stress-activated signal transduction pathways, Herein we present genetic and biochemical studies of the fission yeast Schizosaccharomyces pombe that disprove this hypothesis and indicate that PP2C instead negatively regulates a downstream element of the pathway. First, high expression of PPSC produces phenotypes that are inconsistent with negative regulation of the Wik1-Wis1-Spc1 stress-activated kinase cascade. Second, high expression of PPSC leads to sustained activating tyrosine phosphorylation of Spc1. Third, Spc1-dependent phosphorylation of Atf1, a transcription factor substrate of Spc1, is unaffected by high expression of PP2C, Fourth, high expression of PP2C suppresses Atf1-dependent transcription of a stress-response gene, These studies strongly suggest that PP2C acts down stream of Spc1 kinase in the stress-activated signal transduction pathway.