Feedback inhibition on cell wall integrity signaling by Zds1 involves Gsk3 phosphorylation of a cAMP-dependent protein kinase regulatory subunit
Feedback inhibition on cell wall integrity signaling by Zds1 involves Gsk3 phosphorylation of a cAMP-dependent protein kinase regulatory subunit
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DOI：
10.1074/jbc.m210691200
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发表时间：
2003-06-27
影响因子：
4.8
通讯作者：
Thevelein, JM
中科院分区：
文献类型：
--
作者：
Griffioen, G;Swinnen, S;Thevelein, JM
我们在此报告，芽殖酵母 cAMP 依赖性蛋白激酶 (cAPK) 受热应激控制。研究发现，温度从 30 摄氏度升高到 37 摄氏度会导致其调节亚基 Bcy1 的表达量增加，并且细胞质定位增加。这两种作用都需要位于其定位域的丝氨酸磷酸化。令人惊讶的是，经典的 cAPK 控制过程被发现与 Bcy1 磷酸化无关，表明这些修饰本身不会影响 cAPK 活性。或者，磷酸化可能会将 cAPK 募集到并从而控制 cAPK 靶标的特定子集（可能是新的），这些靶标可能位于核外。 Zds1 和 Zds2 可能在此过程中发挥作用，因为人们发现它们需要在 37°C 下将过度磷酸化的 Bcy1 保留在细胞质中。 Mck1 是哺乳动物糖原合酶激酶 3 的同源物，也是热激活 Pkc1-Slt2/Mpk1 细胞壁完整性通路的下游组件，部分负责 Bcy1 的过度磷酸化。值得注意的是，Zds1 似乎充当细胞壁完整性信号传导的负调节因子，并且这种活性部分依赖于 Bcy1 的磷酸化状态。因此，Bcy1和Zds1的Mck1磷酸化可能对细胞壁完整性信号通路构成前所未有的负反馈控制。
We report here that budding yeast cAMP-dependent protein kinase (cAPK) is controlled by heat stress. A rise in temperature from 30 to 37degreesC was found to result in both a higher expression and an increased cytoplasmic localizationof its regulatory subunit Bcy1. Both of these effects required phosphorylationof serines located in its localization domain. Surprisingly, classic cAPK-controlled processes were found to be independent of Bcy1 phosphorylation, indicating that these modifications do not affect cAPK activity as such. Alternatively, phosphorylation may recruit cAPK to, and thereby control, a specific subsetof ( perhaps novel) cAPK targets that are presumably localized extranuclearly. Zds1 and Zds2 may play a role in this process, since these were found required to retain hyperphosphorylated Bcy1 in the cytoplasm at 37degreesC. Mck1, a homologue of mammalian glycogen synthase kinase 3 and a downstream component ofthe heat-activated Pkc1-Slt2/Mpk1 cell wall integrity pathway, is partly responsible for hyperphosphorylations of Bcy1. Remarkably, Zds1 appears to act as a negative regulator of cell wall integrity signaling, and this activity is dependent in part on the phosphorylation status of Bcy1. Thus, Mck1 phosphorylation of Bcy1 and Zds1 may constitute an unprecedented negative feedback control on the cell wall integrity-signaling pathway.