Yeast Osmosensors Hkr1 and Msb2 Activate the Hog1 MAPK Cascade by Different Mechanisms
Yeast Osmosensors Hkr1 and Msb2 Activate the Hog1 MAPK Cascade by Different Mechanisms
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DOI：
10.1126/scisignal.2004780
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发表时间：
2014-02-25
影响因子：
7.3
通讯作者：
Saito, Haruo
中科院分区：
文献类型：
--
作者：
Tanaka, Keiichiro;Tatebayashi, Kazuo;Saito, Haruo
为了应对环境的高渗透压，出芽酵母酿酒酵母激活丝裂原活化蛋白激酶（MAPK） Hog1，控制一系列渗透适应反应。两个独立但功能冗余的渗透传感系统，包括跨膜传感器组氨酸激酶Sln1或四跨膜蛋白Sho1，刺激Hog1 MAPK级联反应。此外，Sho1信号分支本身也涉及两个功能冗余的渗透传感器Hkr1和Msb2。然而，任何单一的渗透传感器（Sln1， Hkr1或Msb2）都足以实现渗透适应。我们发现Hkr1或Msb2刺激Hog1级联的信号机制对每个渗透传感器都是特异性的。具体来说，Msb2激活Hog1需要支架蛋白Bem1和肌动蛋白细胞骨架。Bem1结合到Msb2的细胞质结构域，从而将Ste20和Cla4激酶募集到膜上，在那里它们中的任何一个都可以激活Ste11激酶。Hkr1的胞质结构域也有助于Ste20激活Ste11，但其机制既不涉及Bem1也不涉及肌动蛋白细胞骨架。此外，我们在Ste20中发现了一个特异性结合到Sho1 SH3 （Src同源3）结构域的PXXP基序。Ste20和Sho1之间的相互作用导致Hkr1激活Hog1，而Msb2则没有。Hkr1和Msb2之间的这些差异可能导致这两种蛋白的差异调控，并提供了一种通过Msb2将细胞骨架调控与渗透胁迫应答联系起来的机制。
To cope with environmental high osmolarity, the budding yeast Saccharomyces cerevisiae activates the mitogen-activated protein kinase (MAPK) Hog1, which controls an array of osmoadaptive responses. Two independent, but functionally redundant, osmosensing systems involving the transmembrane sensor histidine kinase Sln1 or the tetraspanning membrane protein Sho1 stimulate the Hog1 MAPK cascade. Furthermore, the Sho1 signaling branch itself also involves the two functionally redundant osmosensors Hkr1 and Msb2. However, any single osmosensor (Sln1, Hkr1, or Msb2) is sufficient for osmoadaptation. We found that the signaling mechanism by which Hkr1 or Msb2 stimulated the Hog1 cascade was specific to each osmosensor. Specifically, activation of Hog1 by Msb2 required the scaffold protein Bem1 and the actin cytoskeleton. Bem1 bound to the cytoplasmic domain of Msb2 and thus recruited the kinases Ste20 and Cla4 to the membrane where either of them can activate the kinase Ste11. The cytoplasmic domain of Hkr1 also contributed to the activation of Ste11 by Ste20, but through a mechanism that involved neither Bem1 nor the actin cytoskeleton. Furthermore, we found a PXXP motif in Ste20 that specifically bound to the Sho1 SH3 (Src homology 3) domain. This interaction between Ste20 and Sho1 contributed to the activation of Hog1 by Hkr1, but not by Msb2. These differences between Hkr1 and Msb2 may enable differential regulation of these two proteins and provide a mechanism through Msb2 to connect regulation of the cytoskeleton with the response to osmotic stress.