Phosphorylated mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 may not always represent its kinase activity in a rat model of focal cerebral ischemia with or without ischemic preconditioning

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• 作者：T. Takahashi ; G.K. Steinberg ; H. Zhao ; ^{hzhao@stanford.edu}
• 关键词：ischemic preconditioning ; kinase activity ; MAPK ; ERK1/2 ; focal ischemia ; stroke
• 刊名：Neuroscience
• 出版年：2012
• 期刊代码：50_03064522
• 类别：neu
• 出版时间：3 May, 2012
• 卷：209
• 期：Complete
• 页码：155-160
• 文件大小：834 K

摘要

The extracellular signal-regulated kinase (ERK) 1/2 protein requires a dual phosphorylation at conserved threonine and tyrosine residues to be fully activated under normal physiological conditions. Thus, ERK1/2 kinase activity is often defined by the quantity of phosphorylated kinase. However, this may not accurately represent its true activity under certain pathological conditions. We investigated whether ERK1/2 kinase activity is proportional to its phosphorylation state in a rat focal ischemia model with and without rapid ischemic preconditioning. We showed that phosphorylated-ERK1/2 protein levels were increased 2.6卤0.07-fold, and ERK1/2 kinase activity was increased 10.6卤1.9-fold in animals receiving ischemic preconditioning alone without test ischemia compared with sham group (P<0.05, n=6/group), suggesting that phosphorylated-ERK1/2 protein levels represent its kinase activity under these conditions. However, preconditioning plus test ischemia robustly blocked ERK1/2 kinase activity, whereas it increased phosphorylated-ERK1/2 protein levels beyond those receiving test ischemia alone, suggesting that phosphorylated-ERK1/2 protein levels were not representative of actual kinase activity in this pathological condition. In conclusion, protein phosphorylation levels of ERK1/2 do not always correspond to kinase activity, thus, measuring the true kinase activity is essential.