IGF-1 phosphorylates AMPK-alpha subunit in ATM-dependent and LKB1-independent manner

Suzuki, A, Kusakai, G, Kishimoto, A, Shimojo, Y, Ogura, T, Lavin, MF and Esumi, H (2004) IGF-1 phosphorylates AMPK-alpha subunit in ATM-dependent and LKB1-independent manner. Biochemical And Biophysical Research Communications, 324 3: 986-992. doi:10.1016/j.bbrc.2004.09.145

Author Suzuki, A
Kusakai, G
Kishimoto, A
Shimojo, Y
Ogura, T
Lavin, MF
Esumi, H
Title IGF-1 phosphorylates AMPK-alpha subunit in ATM-dependent and LKB1-independent manner
Journal name Biochemical And Biophysical Research Communications   Check publisher's open access policy
ISSN 0006-291X
Publication date 2004-01-01
Sub-type Article (original research)
DOI 10.1016/j.bbrc.2004.09.145
Volume 324
Issue 3
Start page 986
End page 992
Total pages 7
Editor W. Baumeister
Place of publication San Diego, U.S.A.
Publisher Academic Press
Language eng
Subject C1
321204 Mental Health
730204 Child health
Abstract Serine/threonine protein kinase AMP-activated protein kinase (AMPK) is a key metabolic stress-responsive factor that promotes the adaptation of cells to their microenvironment. Elevated concentrations of intracellular AMP, caused by metabolic stress, are known to activate AMPK by phosphorylation of the catalytic subunit. Recently, the tumor suppressor serine/threonine protein kinase LKB1 was identified as an upstream kinases, AMPKKs. In the current study, we found that stimulation with growth factors also caused AMPK-alpha subunit phosphorylation. Interestingly, even an LKB1-nonexpressing cancer cell line, HeLa, exhibited growth factor-stimulated AMPK-alpha subunit phosphorylation, suggesting the presence of an LKB1-independent pathway for AMPK-alpha subunit phosphorylation. In the human pancreatic cancer cell line PANC-1, AMPK-alpha subunit phosphorylation promoted by IGF-I was suppressed by antisense ataxia telangiectasia mutated (ATM) expression. We found that IGF-1 also induced AMPK-alpha subunit phosphorylation in the human normal fibroblast TIG103 cell line, but failed to do so in a human fibroblast AT2-KY cell line lacking ATM. Immunoprecipitates of ATM collected from IGF-1-stimulated cells also caused the phosphorylation of the AMPK-alpha subunit in vitro. IGF-1-stimulated ATM phosphorylation at both threonine and tyrosine residues, and our results demonstrated that the phosphorylation of tyrosine in the ATM molecule is important for AMPK-alpha subunit phosphorylation during IGF-1 signaling. These results suggest that IGF-1 induces AMPK-alpha subunit phosphorylation via an ATM-dependent and LKB1-independent pathway. (C) 2004 Elsevier Inc. All rights reserved.
Keyword Biochemistry & Molecular Biology
Tyrosine Kinase
Tumor Cell Line
Activated Protein-kinase
Fatty-acid Oxidation
Yeast Snf1
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2005 Higher Education Research Data Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 61 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 15 Aug 2007, 13:24:04 EST