Mitogen-activated protein kinase stimulation of Ca2+ signaling is required for survival of endoplasmic reticulum stress in yeast
Mitogen-activated protein kinase stimulation of Ca2+ signaling is required for survival of endoplasmic reticulum stress in yeast
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DOI：
10.1091/mbc.e03-02-0113
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发表时间：
2003-10-01
影响因子：
3.3
通讯作者：
Cunningham, KW
中科院分区：
文献类型：
--
作者：
Bonilla, M;Cunningham, KW
芽殖酵母Saccharomycescerevisiae中的内质网（ER）应激通过由Cch 1和Mid 1组成的质膜通道触发Ca 2+内流。这种反应激活钙调神经磷酸酶，这有助于防止细胞死亡期间多种形式的ER压力，包括对唑类抗真菌药物的反应。在此，我们表明，ER应力激活细胞完整性有丝分裂原激活蛋白激酶级联在酵母和Pkc 1和Mpk 1的激活是必要的刺激Cch 1-Mid 1钙通道独立于许多已知的Mpk 1（Rlm 1，Swi 4，Swi 6，Mih 1，Hsl 1，和Swe 1）。ER应激反应中产生的咪康唑，衣霉素，或其他抑制剂也引发了短暂的G2/M期阻滞，依赖于Swe 1蛋白激酶。钙调神经磷酸酶在Swe 1依赖的细胞周期阻滞中起的作用很小，Swe 1对钙调神经磷酸酶依赖的细胞死亡的避免作用很小。这些发现有助于澄清Mpk 1，钙调神经磷酸酶和Swe 1之间的相互作用，并表明钙细胞存活途径促进药物耐药性独立于未折叠蛋白反应和G2/M细胞周期检查点。
Endoplasmic reticulum (ER) stress in the budding yeast Saccharomyces cerevisiae triggers Ca2+ influx through a plasma membrane channel composed of Cch1 and Mid1. This response activates calcineurin, which helps to prevent cell death during multiple forms of ER stress, including the response to azole-class antifungal drugs. Herein, we show that ER stress activates the cell integrity mitogen-activate protein kinase cascade in yeast and that the activation of Pkc1 and Mpk1 is necessary for stimulation of the Cch1-Mid1 Ca2+ channel independent of many known targets of Mpk1 (Rlm1, Swi4, Swi6, Mih1, Hsl1, and Swe1). ER stress generated in response to miconazole, tunicamycin, or other inhibitors also triggered a transient G2/M arrest that depended upon the Swe1 protein kinase. Calcineurin played little role in the Swe1-dependent cell cycle arrest and Swe1 had little effect on calcineurin-dependent avoidance of cell death. These findings help to clarify the interactions between Mpk1, calcineurin, and Swe1 and suggest that the calcium cell survival pathway promotes drug resistance independent of both the unfolded protein response and the G2/M cell cycle checkpoint.