AICAR induces phosphorylation of AMPK in an ATM-dependent, LKB1-independent manner

Yan Sun, Katie E. Connors, Da Qing Yang

Research output: Contribution to journalArticlepeer-review

101 Scopus citations


AMPK is an AMP-activated protein kinase that plays an important role in regulating cellular energy homeostasis. Metabolic stress, such as heat shock and glucose starvation, causes an energy deficiency in the cell and leads to elevated levels of intracellular AMP. This results in the phosphorylation and activation of AMPK. LKB1, a tumor suppressor, has been identified as an upstream kinase of AMPK. We found that in response to treatment with 5-aminoimidazole-4-carboxamide-1-β-4- ribofuranoside (AICAR), the LKB1 deficient cancer cell line, HeLa, exhibited AMPK-α phosphorylation. This indicates the existence of an LKB1-independent AMPK-α phosphorylation pathway. ATM is a protein that is deficient in the disease ataxia telangiectasia (A-T). We measured the activation of AMPK by AICAR in the normal mouse embryo fibroblast cell line, A29, and the mouse cell line lacking the ATM protein, A38. In A38 cells, the level of AICAR-induced AMPK-alpha; phosphorylation was significantly lower than that found in A29 cells. Furthermore, phosphorylation of AMPK in HeLa and A29 cells was inhibited by an ATM specific inhibitor, KU-55933. Our results demonstrate that AICAR treatment could lead to phosphorylation of AMPK in an ATM-dependent and LKB1-independent manner. Thus, ATM may function as a potential AMPK kinase in response to AICAR treatment.

Original languageEnglish (US)
Pages (from-to)239-245
Number of pages7
JournalMolecular and cellular biochemistry
Issue number1-2
StatePublished - Dec 2007
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgments We would like to thank Dr. Graeme Smith for providing us with the ATM inhibitor, KU-55933. This work was supported by The South Dakota Biomedical Research Infrastructure Network (BRIN) Program of the National Center for Research Resources of NIH (Grant Number: 2-P20-RR016479).


  • AMPK
  • ATM
  • Protein phosphorylation


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