Regulation of stress-activated protein kinase signaling pathway by protein phosphatase 2C (PP2C)

蛋白磷酸酶 2C (PP2C) 对应激激活蛋白激酶信号通路的调节

• 批准号: 14086201
• 负责人: KOBAYASHI Takayasu
• 金额: $ 51.33万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 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/en/grant/KAKENHI-PROJECT-14086201/
• 关键词: protein phosphatase; stress; SAPK; ストレス応答; プロティンホスファターゼ

(1) PP2Cε precipitates in negative regulation of TAK1 and ASK1Ectopic expression of PP2Cε in mammalian cells represses the activity of TAK1 and ASK1, two mitogen-activated protein kinase kinase kinases. PP2Cε keeps these kinases in an inactive state in quiescent cells by associating with and dephosphorylating them. PP2Cε associated with TAK1 and ASK1 in quiescent cells, but the association was transiently suppressed in response to treatment of the cells with IL-1 and H_2_O_2, respectively, which activate these respective kinases. On the basis of these results we proposed that PP2Cε regulates TAK1 and ASK1 pathways by a common regulatory mechanism.(2) PP2Cδ (ILKAP) participates in positive regulation of ASK1In contrast to PP2Cε, PP2Cδ (ILKAP) acts as a positive regulator of TNF induced SAPK signaling. Transient expression of PP2Cδ (ILKAP) in 293 cells enhanced TNF induced activation of JNK and p38. PP2Cδ (ILKAP) associated with ASK1 and this association was enhanced in response to TNF treatment. These results suggested that PP2Cδ (ILKAP) may dephosphorylate inhibitory phosphorylation site(s) of ASK1.(3) JNK negatively regulates PP2CζPP2Cζ, a PP2C family member that is enriched in testicular germ cells, is phosphorylated at Ser92 and Thr202/205 by JNK but not by p38 or ERK both in vivo and in vitro. We show that phosphorylation of PP2Cζ at Ser92 but not at Thr202/205 repressed its phosphatase activity.

(1)PP 2C ε在哺乳动物细胞中的异位表达抑制了两种丝裂原活化蛋白激酶TAK 1和ASK 1的活性。PP 2C ε通过与这些激酶结合并使其去磷酸化，使这些激酶在静止细胞中保持非活性状态。PP 2C ε在静止细胞中与TAK 1和ASK 1相关，但分别用IL-1和H_2_O_2处理细胞时，这种相关性被短暂抑制，IL-1和H_2_O_2分别激活这些相应的激酶。基于这些结果，我们提出PP 2C ε通过共同的调节机制调节TK 1和ASK 1途径。(2)PP 2C δ（ILKAP）参与ASK 1的正向调节与PP 2C ε不同，PP 2C δ（ILKAP）是TNF诱导的SAPK信号的正向调节者。PP 2C δ（ILKAP）在293细胞中的瞬时表达增强了TNF诱导的JNK和p38的活化。PP 2C δ（ILKAP）与ASK 1相关，这种相关性在TNF治疗后增强。这些结果表明，PP 2C δ（ILKAP）可以使ASK 1的抑制性磷酸化位点去磷酸化。(3)JNK负性调节PP 2C β PP 2C β是PP 2C家族成员，在睾丸生殖细胞中富集，在体内和体外均通过JNK而不是p38或ERK在Ser 92和Thr 202/205处磷酸化。我们发现，磷酸化的PP 2C丝氨酸92，但不是在Thr 202/205抑制其磷酸酶活性。

项目成果

Komaki et al.: "Molecular cloning of PP2Ceta, novel member of protein phosphatase 2C family."Biochim.Biophys.Acta. 1630. 130-137 (2003)

Komaki 等人：“蛋白磷酸酶 2C 家族新成员 PP2Ceta 的分子克隆。”Biochim.Biophys.Acta。

Negative regulation of protein phosphatase 2Cb by ISG15 conjugation.

ISG15 缀合对蛋白磷酸酶 2Cb 的负调节。

• 发表时间: 2006
• 期刊: FEBS Letters 580
• 作者: Takeuchi;Tomoharu
• 通讯作者: Tomoharu

哺乳動物細胞プロティンホスファターゼ2Cファミリーメンバーによる細胞機能の調節

哺乳动物细胞蛋白磷酸酶 2C 家族成员对细胞功能的调节

• 发表时间: 2005
• 期刊: 化学と生物 43
• 作者: Keiichiro Takahashi;Satuski Yaegashi;Atsushi Kameda;Masami Hagiya;田村眞理他
• 通讯作者: 田村眞理他

PP2C family members play key roles in regulation of cell survival and apoptosis

• DOI: 10.1111/j.1349-7006.2006.00219.x
• 发表时间: 2006-07
• 期刊: Cancer Science
• 影响因子: 5.7
• 作者: S. Tamura;Shinnosuke Toriumi;J. Saito;K. Awano;Tada-Aki Kudo;Takayasu Kobayashi

Clathrin light chain b is capable of affecting potently a major protein phosphatase from microtubules (MT-PP1).

网格蛋白轻链 b 能够有效影响微管中的主要蛋白磷酸酶 (MT-PP1)。

• 发表时间: 2006
• 期刊: FEBS Lett. 580
• 作者: A.Hiraga;N.Morrice;E.Honda;S.Tamura;H.Munakata
• 通讯作者: H.Munakata