Repression of yeast Ste12 transcription factor by direct binding of unphosphorylated Kss1 MAPK and its regulation by the Ste7 MEK
Repression of yeast Ste12 transcription factor by direct binding of unphosphorylated Kss1 MAPK and its regulation by the Ste7 MEK
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DOI：
10.1101/gad.12.18.2887
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发表时间：
1998-09-15
影响因子：
10.5
通讯作者：
Thorner, J
中科院分区：
文献类型：
--
作者：
Bardwell, L;Cook, JG;Thorner, J
丝裂原活化蛋白激酶（MAPK）Kss 1在调节酿酒酵母的丝状（侵入性）生长中具有双重作用。Kss 1的刺激功能需要其催化活性和MAPK/ERK激酶（MEK）Ste 7的激活;相反，Kss 1的抑制功能两者都不需要。本研究探讨了Kss 1抑制侵入性生长的机制，以及Ste 7的作用如何克服这种抑制。我们发现，未磷酸化的Kss 1直接结合到转录因子Ste 12，这种结合是必要的Kss 1介导的抑制Ste 12，和Ste 7介导的磷酸化Kss 1减弱Kss 1-Ste 12相互作用，并解除Kss 1介导的抑制。相对于Kss 1，MAPK Fus 3与Ste 12的结合强度较低，相应地是侵袭性生长的较弱抑制剂。Kss 1突变体的分析表明，Kss 1的激活环控制与Ste 12的结合。通过与蛋白激酶的未活化同种型的物理相互作用而有效抑制转录因子，并通过激酶的活化而解除这种抑制，是基因表达的信号依赖性调节的新机制。
The mitogen-activated protein kinase (MAPK) Kss1 has a dual role in regulating filamentous (invasive) growth of the yeast Saccharomyces cerevisiae. The stimulatory function of Kss1 requires both its catalytic activity and its activation by the MAPK/ERK kinase (MEK) Ste7; in contrast, the inhibitory function of Kss1 requires neither. This study examines the mechanism by which Kss1 inhibits invasive growth, and how Ste7 action overcomes this inhibition. We found that unphosphorylated Kss1 binds directly to the transcription factor Ste12, that this binding is necessary for Kss1-mediated repression of Ste12, and that Ste7-mediated phosphorylation of Kss1 weakens Kss1-Ste12 interaction and relieves Kss1-mediated repression. Relative to Kss1, the MAPK Fus3 binds less strongly to Ste12 and is correspondingly a weaker inhibitor of invasive growth. Analysis of Kss1 mutants indicated that the activation loop of Kss1 controls binding to Ste12. Potent repression of a transcription factor by its physical interaction with the unactivated isoform of a protein kinase, and relief of this repression by activation of the kinase, is a novel mechanism for signal-dependent regulation of gene expression.