PD98059 and U0126 activate AMP-activated protein kinase by increasing the cellular AMP:ATP ratio and not via inhibition of the MAP kinase pathway

被引：62

作者：

Dokladda, K ^{[1
]}

Green, KA ^{[1
]}

Pan, DA ^{[1
]}

Hardie, DG ^{[1
]}

机构：

[1] Univ Dundee, Wellcome Trust Bioctr, Div Mol Physiol, Dundee DD1 5EH, Scotland

来源：

FEBS LETTERS | 2005年 / 579卷 / 01期

基金：

英国惠康基金;

关键词：

AMP-activated protein kinase; PD98059; U0126; PD184352; ERK1/ERK2; MAP kinase;

D O I：

10.1016/j.febslet.2004.11.084

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：236 / 240

页数：5

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