文章摘要
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:2019-05-18
DOI:
中文关键词: MAPKs  MKPs  激活  催化
英文关键词: MAPKs  MKPs  Carboxyl-terminal Domain  Catalysis
基金项目:
作者单位邮编
刘文桐* 清华大学生命科学学院 北京 中国 100084
  
徐荣 苏州大学医学院 江苏 苏州 中国 
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中文摘要:
      目的:丝裂原活化蛋白激酶 (Mitogen-activated Protein Kinases, MAPK) 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MAPK的信号传递。在MKPs去磷酸化MAPKs的过程中,MAPK同时会激活部分MKPs的催化能力,MKP1便是其中之一。本文比较三种经典MAPKs底物,ERK、JNK和p38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p38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的激活程度。结果: ERK2和JNK1能够激活MKP1,催化速率达至原本的2倍,而ERK2与MKP1的结合力比JNK弱约6倍; p38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,ERK和JNK能够激活MKP1催化活力,而p38则没有激活效果,进一步阐述了MAPKs 和MKPs间的特异性相互作用,以及对其活力的影响。
英文摘要:
      Objective: MAPK (Mitogen-activated Protein Kinases) is a pivotal pathway of cellular signal transduction, it is dephosphorylated by MKPs (Mitogen-activate Protein Kinase Phosphatases), the latter negatively regulate MAPK 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, ERK, JNK and p38, are compared with their activation on MKP1 catalysis, facilitate understanding of substrate selective mechanisms between MAPKs and MKPs. Method(s): Use small molecular pNPP as substrate, adjust concentrations of present unphosphorylated ERK2, JNK1 and p38 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. Result(s): ERK2 and JNK1 activates MKP1, its catalytic velocities are risen to twice, but binding affinity of ERK2 to MKP1 is 6 times weaker than that of JNK. No activated effects observed by p38 to MKP1 dephosphorylated activities. Conclusion(s): Among three typical MAPKs, ERK and JNK can activate MKP1 catalytic activities, but p38 has no activated effects, providing an insight into features of MAPKs and MKPs interactions and impacts on catalytic activities.
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