PD98059 and U0126 activate AMP-activated protein kinase by increasing the cellular AMP:ATP ratio and not via inhibition of the MAP kinase pathway
PD98059 and U0126 activate AMP-activated protein kinase by increasing the cellular AMP:ATP ratio and not via inhibition of the MAP kinase pathway
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DOI：
10.1016/j.febslet.2004.11.084
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发表时间：
2005-01-03
期刊：
影响因子：
3.5
通讯作者：
Hardie, DG
中科院分区：
文献类型：
--
作者：
Dokladda, K;Green, KA;Hardie, DG
MAP激酶通路抑制剂U0126在HEK293细胞中引起AMP活化蛋白激酶（AMPK）的磷酸化和活化，并增加其下游靶乙酰辅酶A羧化酶的磷酸化。这种效应仅发生在表达上游激酶LKB 1的细胞中。在另外两种广泛使用的MAP激酶途径抑制剂中，PD98059在结构上与U0126没有密切关系，但PD184352却不能激活AMPK。U0126和PD98059，而不是PD184352，也增加了细胞ADP：ATP和AMP：ATP的比例，解释了它们激活AMPK的能力。这些结果表明，在解释使用U0126和PD98059进行的实验时需要谨慎。(C)2004年由Elsevier B.V.代表欧洲生物化学学会联合会出版。
The MAP kinase pathway inhibitor U0126 caused phosphorylation and activation of AMP-activated protein kinase (AMPK) and increased phosphorylation of its downstream target acetyl-CoA carboxylase, in HEK293 cells. This effect only occurred in cells expressing the upstream kinase, LKB1. Of two other widely used MAP kinase pathway inhibitors not closely related in structure to U0126, PD98059 also activated AMPK but PD184352 did not. U0126 and PD98059, but not PD184352, also increased the cellular ADP:ATP and AMP:ATP ratios, accounting for their ability to activate AMPK. These results suggest the need for caution in interpreting experiments conducted using U0126 and PD98059. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.