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PD98059 and U0126 activate AMP‐activated protein kinase by increasing the cellular AMP:ATP ratio and not via inhibition of the MAP kinase pathway
Author(s) -
Dokladda Kanchana,
Green Kevin A.,
Pan David A.,
Hardie D. Grahame
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.11.084
Subject(s) - ampk , mitogen activated protein kinase kinase , chemistry , protein kinase a , map kinase kinase kinase , microbiology and biotechnology , cyclin dependent kinase 9 , amp activated protein kinase , phosphorylation , ask1 , kinase , map2k7 , cyclin dependent kinase 2 , biochemistry , biology
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.