The role of docking interactions in mediating signaling input, output, and discrimination in the yeast MAPK network
The role of docking interactions in mediating signaling input, output, and discrimination in the yeast MAPK network
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DOI：
10.1016/j.molcel.2005.10.030
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发表时间：
2005-12-22
期刊：
影响因子：
16
通讯作者：
Lim, WA
中科院分区：
文献类型：
--
作者：
Reményi, A;Good, MC;Lim, WA
细胞使用丝裂原活化蛋白激酶（MAPKs）网络来协调对各种细胞外信号的反应。在这里，我们研究了对接相互作用在确定酵母MAPKs Fus3和Kss1的连通性中的作用。这些密切相关的激酶被共同的上游MAPK激酶Ste7激活，但分别产生不同的输出反应，交配和丝状生长。我们发现对接相互作用对于与激酶的通信是必要的，并且它们可以编码通路特异性输入和输出的细微差异。细胞周期阻滞介质Far1是一种交配特异性底物，具有选择性结合Fus3的对接基序。相比之下，共享伴侣Ste7有一个混杂的基序，可以结合Fus3和Kss1。结构分析表明Fus3以不同的构象模式与特异性肽和混杂肽相互作用。诱导匹配识别可能允许对接肽通过利用激酶柔韧性的细微差异来实现歧视。
Cells use a network of mitogen-activated protein kinases (MAPKs) to coordinate responses to diverse extracellular signals. Here, we examine the role of docking interactions in determining connectivity of the yeast MAPKs Fus3 and Kss1. These closely related kinases are activated by the common upstream MAPK kinase Ste7 yet generate distinct output responses, mating and filamentous growth, respectively. We find that docking interactions are necessary for communication with the kinases and that they can encode subtle differences in pathway-specific input and output. The cell cycle arrest mediator Far1, a mating-specific substrate, has a docking motif that selectively binds Fus3. In contrast, the shared partner Ste7 has a promiscuous motif that binds both Fus3 and Kss1. Structural analysis reveals that Fus3 interacts with specific and promiscuous peptides in conformationally distinct modes. Induced fit recognition may allow docking peptides to achieve discrimination by exploiting subtle differences in kinase flexibility.