The PP2C Alphabet Is a Negative Regulator of Stress-Activated Protein Kinase Signaling in Drosophila
The PP2C Alphabet Is a Negative Regulator of Stress-Activated Protein Kinase Signaling in Drosophila
复制标题
DOI：
10.1534/genetics.108.096461
复制
发表时间：
2009-02-01
期刊：
影响因子：
3.3
通讯作者：
Therrien, Marc
中科院分区：
文献类型：
--
作者：
Baril, Caroline;Sahmi, Malha;Therrien, Marc
Jun N-末端激酶和1338通路，也称为应激激活蛋白激酶（SAPK）通路，是贯穿后生动物的发育和成年生活的粘附性地使用的信号传导管道，其中它们在细胞凋亡、免疫功能和环境应激反应的控制中发挥核心作用。我们最近发现了一种PP 2C家族的果蝇Ser/Thr磷酸酶，命名为Alphabet（Alph），它是Ras/ERK通路的负调节因子。在这里，我们表明，阿尔法也发挥了抑制作用，就果蝇SAPK信号在发展过程中，以及在应激条件下，如氧化或遗传毒性应激。上位性实验表明，α作用于MAPKKs Hep和Lic上游的一个步骤。与此解释一致，生化实验确定上游MAPKKKs Slpr，Tak 1和Wnd作为推定的底物。与以前的研究结果一起，这项工作确定了Alph作为果蝇MAPK信号的一般衰减剂。
The Jun N-terminal kinase and 1338 pathways, also known as stress-activated protein kinase (SAPK) pathways, are signaling conduits reiteratively used throughout the development and adult life of metazoans where they play central roles in the control of apoptosis, immune function, and environmental stress responses. We recently identified a Drosophila Ser/Thr phosphatase of the PP2C family, named Alphabet (Alph), which acts as a negative regulator of the Ras/ERK pathway. Here we show that Alph also plays an inhibitory role with respect to Drosophila SAPK signaling during development as well as under stress conditions such as oxidative or genotoxic stresses. Epistasis experiments suggest that Alph acts at a Step upstream of the MAPKKs Hep and Lic. Consistent with this interpretation, biochemical experiments identify the upstream MAPKKKs Slpr, Tak1, and Wnd as putative substrates. Together with previous findings, this work identifies Alph as a general attenuator of MAPK signaling in Drosophila.