A conserved protein interaction network involving the yeast MAP kinases Fus3 and Kss1
A conserved protein interaction network involving the yeast MAP kinases Fus3 and Kss1
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DOI：
10.1083/jcb.200310021
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发表时间：
2004-01-19
影响因子：
7.8
通讯作者：
Bardwell, L
中科院分区：
文献类型：
--
作者：
Kusari, AB;Molina, DM;Bardwell, L
酿酒酵母丝裂原活化蛋白激酶（MAPK）Fus 3和Kss 1与多种调节因子和底物结合。我们发现，在这些MAPK（CD/7 Rn区域）中的保守对接位点的突变破坏了与其结合伙伴的重要子集的结合，包括Ste 7 MAPK激酶，Ste 5接头/支架蛋白，以及Dig 1和Dig 2转录抑制因子。支持Ste 5和Ste 7与MAPK的相同区域结合的可能性，它们部分竞争Fus 3结合。在体内，一些MAPK突变体显示减少Ste 7依赖的磷酸化，并且所有这些突变体在交配和信息素反应中表现出多种缺陷。Kss 1突变体也有缺陷的Kss 1强加的Ste 12的镇压。我们的结论是，MAPKs包含一个结构和功能上保守的对接位点，介导了一个整体的积极作用网络的相互作用与同源对接位点的监管机构和基板。这种相互作用网络的关键特征似乎从酵母到人类都是保守的。
The Saccharomyces cerevisiae mitogen-activated protein kinases (MAPKs) Fus3 and Kss1 bind to multiple regulators and substrates. We show that mutations in a conserved docking site in these MAPKs (the CD/7rn region) disrupt binding to an important subset of their binding partners, including the Ste7 MAPK kinase, the Ste5 adaptor/scaffold protein, and the Dig1 and Dig2 transcriptional repressors. Supporting the possibility that Ste5 and Ste7 bind to the same region of the MAPKs, they partially competed for Fus3 binding. In vivo, some of the MAPK mutants displayed reduced Ste7-dependent phosphorylation, and all of them exhibited multiple defects in mating and pheromone response. The Kss1 mutants were also defective in Kss1-imposed repression of Ste12. We conclude that MAPKs contain a structurally and functionally conserved docking site that mediates an overall positively acting network of interactions with cognate docking sites on their regulators and substrates. Key features of this interaction network appear to have been conserved from yeast to humans.