Cdc37p is required for stress-induced high-osmolarity glycerol and protein kinase C mitogen-activated protein kinase pathway functionality by interaction with Hog1p and Slt2p (Mpk1p)v
Cdc37p is required for stress-induced high-osmolarity glycerol and protein kinase C mitogen-activated protein kinase pathway functionality by interaction with Hog1p and Slt2p (Mpk1p)v
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DOI：
10.1128/ec.00343-06
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发表时间：
2007-03-01
期刊：
影响因子：
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通讯作者：
van der Vies, Saskia M.
中科院分区：
文献类型：
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作者：
Hawle, Patricija;Horst, Danielle;van der Vies, Saskia M.
酿酒酵母利用快速反应的丝裂原活化蛋白激酶(MAPK)信号通路来有效地适应不断变化的环境。在这里，我们报道了酪蛋白激酶2对Hsp90辅伴蛋白CDC37P的磷酸化，控制了酵母中两个MAPK级联的功能。这些途径，高渗透压甘油(HOG)途径和细胞完整性(蛋白激酶C)MAPK途径，分别介导对高渗透胁迫和细胞壁胁迫的适应性反应。CDC37P中磷酸化位点Ser14的突变使细胞对渗透胁迫和钙荧光白色的细胞壁扰动敏感。我们发现，在cdc37-S14A突变体中，细胞中MAPKs Hog1p和SLt2p(Mpk1p)的水平降低，从而抑制了Hog1p和SLt2p介导的下游反应。此外，我们还提供了证据表明，Hog1p和SLt2p都在体内与Cdc37p形成了一个复合体，这是以前没有报道的。Hsp90、slt2p和Hog1p与CDc37p的相互作用取决于其磷酸化状态。事实上，我们的生化数据表明，CDC37-S14A突变体的渗透敏感性表型是由于失去了CDC37P、Hog1p和Hsp90之间的相互作用。同样，在细胞壁胁迫过程中，slt2p与CDc37p和Hsp90的相互作用对于slt2p依赖的下游反应至关重要，例如转录因子Rlm1p的激活。有趣的是，磷酸化的SLt2p，而不是磷酸化的Hog1p，与Cdc37p的亲和力增加。综上所述，这些观察结果表明，CDC37P作为MAPK信号的调节因子。
The yeast Saccharomyces cerevisiae utilizes rapidly responding mitogen-activated protein kinase (MAPK) signaling cascades to adapt efficiently to a changing environment. Here we report that phosphorylation of Cdc37p, an Hsp90 cochaperone, by casein kinase 2 controls the functionality of two MAPK cascades in yeast. These pathways, the high-osmolarity glycerol (HOG) pathway and the cell integrity (protein kinase C) MAPK pathway, mediate adaptive responses to high osmotic and cell wall stresses, respectively. Mutation of the phosphorylation site Ser14 in Cdc37p renders cells sensitive to osmotic stress and cell wall perturbation by calcofluor white. We found that levels of the MAPKs Hog1p and Slt2p (Mpk1p) in cells are reduced in a cdc37-S14A mutant, and consequently downstream responses mediated by Hog1p and Slt2p are compromised. Furthermore, we present evidence that Hog1p and Slt2p both interact in a complex with Cdc37p in vivo, something that has not been reported previously. The interaction of Hsp90, Slt2p, and Hog1p with Cdc37p depends on the phosphorylation status of Cdc37p. In fact, our biochemical data show that the osmosensitive phenotype of the cdc37-S14A mutant is due to the loss of the interaction between Cdc37p, Hog1p, and Hsp90. Likewise, during cell wall stress, the interaction of Slt2p with Cdc37p and Hsp90 is crucial for Slt2p-dependent downstream responses, such as the activation of the transcription factor Rlm1p. Interestingly, phosphorylated Slt2p, but not phosphorylated Hog1p, has an increased affinity for Cdc37p. Together these observations suggest that Cdc37p acts as a regulator of MAPK signaling.