| 刘文桐,郭国光,何倩倩,徐 荣,何青霞.MAPKs对磷酸酶MKP1-CD催化的激活作用研究[J].,2019,19(18):3401-3404 |
| MAPKs对磷酸酶MKP1-CD催化的激活作用研究 |
| Effects of MAPKs Activation on MKP1-CD Catalysis |
| 投稿时间：2019-05-15 修订日期：2019-06-09 |
| DOI：10.13241/j.cnki.pmb.2019.18.001 |
| 中文关键词: 丝裂原活化蛋白激酶 双位点特异性磷酸酶 催化结构域 激活 |
| 英文关键词: MAPKs MKPs Catalytic Activation |
| 基金项目:国家自然科学基金项目（31770841） |
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| 中文摘要: |
| 摘要 目的：丝裂原活化蛋白激酶 (Mitogen-activated Protein Kinases, MAPKs) 是细胞内重要的信号传导通路，双位点特异性磷酸酶 (Mitogen-activated Protein Kinase Phosphatases, MKPs) 去磷酸化MAPKs，负调控MAPKs的信号传递。在MKPs去磷酸化MAPKs的过程中，MAPKs同时会激活部分MKPs的催化能力，MKP1便是其中之一。本文旨在比较三种经典MAPKs底物，ERK2、JNK1和p38α对MKP1磷酸酶催化能力的激活效果，进一步理解MAPKs与MKP1的底物特异性机制。方法：以pNPP为底物，检测在不同浓度的非磷酸化 ERK2、JNK1和p38α存在下，MKP1-CD催化结构域片段蛋白质去磷反应速度的变化，对比所得的动力学参数以确定MAPKs对MKP1激活程度的差异。结果：ERK2和JNK1能够激活MKP1的催化活力，将催化速率提升1.5 ~ 2倍，而ERK2与MKP1的结合力比JNK1弱约6倍； p38α则没有观察到对MKP1去磷酸化能力的激活效果。结论：三种经典MAPKs中，ERK2和JNK1能够激活MKP1催化活力，而p38α则无法激活MKP1，进一步揭示了MAPKs 和MKPs间的特异性相互作用，以及底物对MKPs活力的影响。 |
| 英文摘要: |
| ABSTRACT Objective: MAPKs (Mitogen-activated Protein Kinases) are pivotal pathways of cellular signal transduction, they are dephosphorylated by MKPs (Mitogen-activate Protein Kinase Phosphatases), the latter negatively regulate MAPKs signal delivery. During reactions of MKPs dephosphorylating MAPKs, MAPKs activate some MKPs catalytic abilities in turn. MKP1 is one of MKPs that can be activated by MAPKs. In this study, three typical MAPKs, ERK2, JNK1 and p38α, are compared with their activation on MKP1 catalysis to facilitate understanding the substrate selective mechanisms between MAPKs and MKPs. Methods: Use small molecular pNPP as substrate, adjust concentrations of present unphosphorylated ERK2, JNK1 and p38α to determine different reactive velocities of MKP1 catalytic-domain fragments if catalytic velocities change. Compare and analyze enzymatic kinetic parameters to identify MAPKs activations on MKP1-CD catalytic activities. Results: ERK2 and JNK1 can activate the catalytic capacity of MKP1 and increase catalytic rates by 1.5 to 2 times, but binding affinity of ERK2 to MKP1 is 6 times weaker than that of JNK1. No activated effects observed by p38α to MKP1 dephosphorylated activities. Conclusion: Among three typical MAPKs, MKP1 can be activated by ERK2 and JNK1, but not p38α, which further reveals specific interactions between MAPKs and MKPs as well as substrate impacts on MKPs catalytic activities. |
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