Dynamic control of yeast MAP kinase network by induced association and dissociation between the Ste50 scaffold and the Opy2 membrane anchor.
Dynamic control of yeast MAP kinase network by induced association and dissociation between the Ste50 scaffold and the Opy2 membrane anchor.
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DOI：
10.1016/j.molcel.2010.09.011
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发表时间：
2010-10
期刊：
影响因子：
16
通讯作者：
Katsuyoshi Yamamoto;K. Tatebayashi;Keiichiro Tanaka;H. Saito
中科院分区：
文献类型：
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作者：
Katsuyoshi Yamamoto;K. Tatebayashi;Keiichiro Tanaka;H. Saito
Ste 11 MAPKKK的膜定位对于丝状生长/侵袭性生长（FG/IG）MAP激酶（MAPK）途径和细胞调节HOG MAPK途径的SHO 1分支的激活是必需的，并且通过Ste 50支架蛋白与Opy 2膜锚的结合来介导。我们发现，Opy 2有两个主要的（CR-A和CR-B），和一个次要的（CR-D），Ste 50的结合位点。CR-A与Ste 50组成型结合，可将信号传递给Hog 1和Fus 3/Kss 1 MAPK。相比之下，CR-B仅在富含葡萄糖的条件下Opy 2被Yck 1/Yck 2磷酸化时结合Ste 50，并优先将信号传递给Hog 1 MAPK。通过活化的Hog 1/Fus 3/Kss 1 MAPK的Ste 50磷酸化通过使Ste 50与Opy 2解离而下调HOG MAPK通路。此外，Ste 50磷酸化与MAPK特异性蛋白磷酸酶一起降低HOG和交配MAPK途径的基础活性。因此，Ste 50-Opy 2相互作用的动态调节微调MAPK信号网络。
Membrane localization of the Ste11 MAPKKK is essential for activation of both the filamentous growth/invasive growth (FG/IG) MAP kinase (MAPK) pathway and the SHO1 branch of the osmoregulatory HOG MAPK pathway, and is mediated by binding of the Ste50 scaffold protein to the Opy2 membrane anchor. We found that Opy2 has two major (CR-A and CR-B), and one minor (CR-D), binding sites for Ste50. CR-A binds Ste50 constitutively and can transmit signals to both the Hog1 and Fus3/Kss1 MAPKs. CR-B, in contrast, binds Ste50 only when Opy2 is phosphorylated by Yck1/Yck2 under glucose-rich conditions and transmits the signal preferentially to the Hog1 MAPK. Ste50 phosphorylation by activated Hog1/Fus3/Kss1 MAPKs downregulates the HOG MAPK pathway by dissociating Ste50 from Opy2. Furthermore, Ste50 phosphorylation, together with MAPK-specific protein phosphatases, reduces the basal activity of the HOG and the mating MAPK pathways. Thus, dynamic regulation of Ste50-Opy2 interaction fine-tunes the MAPK signaling network.