The MAP kinase (MAPK) Hog1 is the central regulator of osmoadaptation in yeast. When cells are exposed to high osmolarity, the functionally redundant Sho1 and Sln1 osmosensors, respectively, activate the Ste11-Pbs2-Hog1 MAPK cascade and the Ssk2/Ssk22-Pbs2-Hog1 MAPK cascade. In a canonical MAPK cascade, a MAPK kinase kinase (MAP3K) activates a MAPK kinase (MAP2K) by phosphorylating two conserved Ser/Thr residues in the activation loop. Here, we report that the MAP3K Ste11 phosphorylates only one activating phosphorylation site (Thr-518) in Pbs2, whereas the MAP3Ks Ssk2/Ssk22 can phosphorylate both Ser-514 and Thr-518 under optimal osmostress conditions. Mono-phosphorylated Pbs2 cannot phosphorylate Hog1 unless the reaction between Pbs2 and Hog1 is enhanced by osmostress. The lack of the osmotic enhancement of the Pbs2-Hog1 reaction suppresses Hog1 activation by basal MAP3K activities and prevents pheromone-to-Hog1 crosstalk in the absence of osmostress. We also report that the rapid-and-transient Hog1 activation kinetics at mildly high osmolarities and the slow and prolonged activation kinetics at severely high osmolarities are both caused by a common feedback mechanism.

中文翻译：

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渗透压通过单磷酸化的Pbs2 MAP2K增强Hog1 MAP激酶的激活磷酸化。

MAP激酶（MAPK）Hog1是酵母中渗透适应的中央调节剂。当细胞暴露于高渗透压时，功能上冗余的Sho1和Sln1渗透传感器分别激活Ste11-Pbs2-Hog1 MAPK级联和Ssk2 / Ssk22-Pbs2-Hog1 MAPK级联。在典型的MAPK级联反应中，MAPK激酶激酶（MAP3K）通过使激活环中的两个保守Ser / Thr残基磷酸化来激活MAPK激酶（MAP2K）。在这里，我们报告MAP3K Ste11仅磷酸化Pbs2中的一个激活磷酸化位点（Thr-518），而MAP3K Ssk2 / Ssk22可以在最佳渗透压条件下磷酸化Ser-514和Thr-518。除非渗透压增强了Pbs2和Hog1之间的反应，否则单磷酸化的Pbs2不能磷酸化Hog1。Pbs2-Hog1反应的渗透性增强的缺乏抑制了基础MAP3K活性对Hog1的激活，并在没有渗压的情况下防止了信息素与Hog1的串扰。我们还报告了在适度高渗透压下的快速和瞬时Hog1激活动力学和在极高渗透压下的缓慢和长时间的激活动力学都是由共同的反馈机制引起的。