Regulatory mechanisms of the environmental stress-responsive MAP kinase signal pathway

环境应激响应MAP激酶信号通路的调控机制

• 批准号: 14104021
• 负责人: SAITO Haruo
• 金额: $ 72.55万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (S)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14104021/
• 关键词: intracellular signal transduction; stress response; MAP kinase; human cultured cells; budding yeast; 分子生物学; 細胞生物学

1) Functional roles and regulation of human stress-activated MAP kinase signal transduction pathway.We identified a novel docking interaction between stress-activated MAPKKK (SAP3K) and stress-activated MAPKK (SAP2K). We also found that a C-terminal region in SAP2K, termed the DVD domain, is essential for this interaction, and elucidated its role in SAP2K activation. Using the specific interaction through DVD domain, we developed a new FRET probe to visualize SAP3K activity in single living cells. Furthermore, we revealed the mechanism of MTK1 activation by the stress-inducible Gadd45 proteins. Gadd45 binds to the N-terminal region of MTK1 SAP3K, induces an N-C dissociation in. MTK1 molecule, and thus facilitates MTK1 dimerization that leads to MTK1 activation by auto-phosphorylation.2) Functional roles and regulation of yeast stress-activated MAP kinase signal transduction pathway.We identified a specific docking interaction between yeast osmoregulatory Ssk2 SAP3K and Pbs2 SAP2K, and revealed that the interaction is essential for specific activation of Pbs2 by Ssk2. We found that the membrane protein Sho1, the cytoplasmic protein Ste50, and the small G-protein Cdc42 bind, serve as adaptor proteins in yeast osmoregulatory Hog1 MAPK pathway. We also revealed that the mucin-like membrane glycoproteins Hkr1 and Msb2 are putative osmosensors in the Sho1 branch of Hog1 MAPK pathway. We proposed that external osmostress causes a conformation change in the mucin domains of Hkrl/Msb2, and thus induces an interaction between Sho1 and Hkrl/Msb2 to activate the Hog1 MAPK pathway.

1）功能作用和人力应激激活的MAP激酶信号转导途径的调节。我们确定了应力激活的MAPKKK（SAP3K）（SAP3K）和压力激活的MAPKK（SAP2K）之间的新型对接相互作用。我们还发现，称为DVD结构域的SAP2K中的C末端区域对于这种相互作用至关重要，并阐明了其在SAP2K激活中的作用。使用通过DVD结构域的特定相互作用，我们开发了一种新的FRET探针来可视化单个活细胞中的SAP3K活性。此外，我们揭示了应力诱导的GADD45蛋白的MTK1激活的机制。 GADD45与MTK1 SAP3K的N末端区域结合，在MTK1分子中诱导N-C解离，从而促进MTK1二聚体，从而导致MTK1通过自磷酸化导致MTK1激活。 Osmoregulation SSK2 SAP3K和PBS2 SAP2K，并揭示了这种相互作用对于SSK2对PBS2的特异性激活至关重要。我们发现，膜蛋白SHO1，细胞质蛋白Ste50和小的G蛋白Cdc42结合，在酵母Osmoregulatory Hog1 MAPK途径中用作衔接蛋白。我们还透露，粘蛋白样膜糖蛋白HKR1和MSB2是HOG1 MAPK途径的SHO1分支中的推定的Osmosentor。我们提出，外部渗透压会导致HKRL/MSB2的粘蛋白结构域的构象变化，从而诱导SHO1和HKRL/MSB2之间的相互作用以激活HOG1 MAPK途径。

项目成果

Transmembrane mucins Hkr1 and Msb2 are putative osmosensors in the SHO1 branch of yeast HOG pathway

• DOI: 10.1038/sj.emboj.7601796
• 发表时间: 2007-08-08
• 期刊: EMBO JOURNAL
• 影响因子: 11.4
• 作者: Tatebayashi, Kazuo;Tanaka, Keiichiro;Saito, Haruo
• 通讯作者: Saito, Haruo

Mita, Hiroaki: "Regulation of MTK1/MEKK4 kinase activity by its N-terminal autoinhibitory domain and GADD45 binding"Molecular and Cellular Biology. 22. 4544-4555 (2002)

Mita、Hiroaki：“MTK1/MEKK4 激酶活性通过其 N 端自抑制结构域和 GADD45 结合进行调节”《分子和细胞生物学》。

Transmembrane mucins Hkrl and Msb2 are putative osmosensors in the SHO1 branch of yeast HOG pathway.

跨膜粘蛋白 Hkrl 和 Msb2 是酵母 HOG 途径 SHO1 分支中假定的渗透传感器。

• 发表时间: 2007
• 期刊: The EMBO Journal 26
• 作者: Tatebayashi;Kazuo
• 通讯作者: Kazuo

The Sln1-Ypol-Ssk1 multistep phosphorelay system that regulates an osmosensing MAP kinase cascade in yeast

Sln1-Ypol-Ssk1 多步磷酸中继系统调节酵母中的渗透感应 MAP 激酶级联

• 发表时间: 2003
• 期刊: Histidine kinases in signal transduction, edited by Inouye, M., and Dutta, R., Academic Press, San Diego
• 作者: Saito;Haruo
• 通讯作者: Haruo

Activation of MTK1/MEKK4 by GADD45 through induced N-C dissociation and dimerization-mediated trans autophosphorylaion of the MTK1 kinase domain.

GADD45 通过诱导 N-C 解离和二聚化介导的 MTK1 激酶结构域反式自磷酸化来激活 MTK1/MEKK4。

• 发表时间: 2007
• 期刊: Molecular and Cellular Biology 27
• 作者: Miyake;Zenshi
• 通讯作者: Zenshi