最新Cell特刊文章

　　

生物通报道，每一期的《Cell》杂志都会评出一篇特刊文章来，本期《Cell》特刊文章由来自加州大学细胞与分子药理学系，生物科学工程系的研究者写的文章，标题为：The Ste5 Scaffold Directs Mating Signaling by Catalytically Unlocking the Fus3 MAP Kinase for Activation。

 

文章通讯作者是来自加州大学细胞与分子药理学系与生物化学与生物生理学系的教授，Wendell Lim，在哈佛大学获得学士学位，在麻省理工获得博士学位，博士后在耶鲁大学读。

 

在酵母的有性繁殖过程中，支架蛋白Ste5具有重要的信号转导作用，对细胞分离素（丝裂原）活化蛋白激酶（mitogen-activated protein kinase，MAPK），Fus3具有重要的调控作用。支架蛋白一直被认为具有拉近酶与酶底物的作用。先前的研究认为，Ste5上Fus3结合位点被认为不具备信号转导的作用，表明Fus3是通过MAPKK Ste7来激活的。

 

研究者在活体外的重组MAPK信号通路，结果发现Fus3是Ste7固有的弱势底物，强的底物是Kss1。研究发现Ste5的某个结构具有激活Fus3的能力，主要通过Ste7的磷酸化作用来实现。这个活性区域能选择性增强Ste7-Fus3磷酸化作用，但无法激活Ste7-Kss1的磷酸化作用。这些结果表明，Fus3具有选择性的活性，主要依赖Ste7来实现。

 

全文免费链接地址：http://www.cell.com/fulltext/S0092-8674(09)00134-2

 

生物通推荐原文检索：The Ste5 Scaffold Directs Mating Signaling by Catalytically Unlocking the Fus3 MAP Kinase for Activation

【Abstract】

The scaffold protein Ste5 is required to properly direct signaling through the yeast mating pathway to the mitogen-activated protein kinase (MAPK), Fus3. Scaffolds are thought to function by tethering kinase and substrate in proximity. We find, however, that the previously identified Fus3-binding site on Ste5 is not required for signaling, suggesting an alternative mechanism controls Fus3's activation by the MAPKK Ste7. Reconstituting MAPK signaling invitro, we find that Fus3 is an intrinsically poor substrate for Ste7, although the related filamentation MAPK, Kss1, is an excellent substrate. We identify and structurally characterize a domain in Ste5 that catalytically unlocks Fus3 for phosphorylation by Ste7. This domain selectively increases the kcat of Ste7Fus3 phosphorylation but has no effect on Ste7Kss1 phosphorylation. The dual requirement for both Ste7 and this Ste5 domain in Fus3 activation explains why Fus3 is selectively activated by the mating pathway and not by other pathways that also utilize Ste7.