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Cited by 183

The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.

AMP-activated protein kinase phosphorylates transcription factors of the CREB family

Open access
Thomson, D. M., Herway, S. T., Fillmore, N., Kim, H., Brown, J. D., Barrow, J. R., Winder, W. W.·2008·Journal of Applied Physiology

Abstract

AMP-activated protein kinase (AMPK) has been identified as a regulator of gene transcription, increasing mitochondrial proteins of oxidative metabolism as well as hexokinase expression in skeletal muscle. In mice, muscle-specific knockout of LKB1, a component of the upstream kinase of AMPK, prevents contraction- and 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR)-induced activation of AMPK in skeletal muscle, and the increase in hexokinase II protein that is normally observed with chronic AICAR activation of AMPK. Since previous reports show a cAMP response element in the promoter region of the hexokinase II gene, we hypothesized that the cAMP-response element (CRE) binding protein (CREB) family of transcription factors could be targets of AMPK. Using radioisotopic kinase assays, we found that recombinant and rat liver and muscle AMPK phosphorylated CREB1 at the same site as cAMP-dependent protein kinase (PKA). AMPK was also found to phosphorylate activating transcription factor 1 (ATF1), CRE modulator (CREM), and CREB-like 2 (CREBL2), but not ATF2. Treatment of HEK-293 cells stably transfected with a CREB-driven luciferase reporter with AICAR increased luciferase activity approximately threefold over a 24-h time course. This increase was blocked with compound C, an AMPK inhibitor. In addition, AICAR-induced activation of AMPK in incubated rat epitrochlearis muscles resulted in an increase in both phospho-acetyl-CoA carboxylase and phospho-CREB. We conclude that CREB and related proteins are direct downstream targets for AMPK and are therefore likely involved in mediating some effects of AMPK on expression of genes having a CRE in their promoters.

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Metadata

Authors
Thomson, D. M., Herway, S. T., Fillmore, N., Kim, H., Brown, J. D., Barrow, J. R., & Winder, W. W.
Venue
Journal of Applied Physiology
Published
2008-02
Volume
104
Issue
2
Pages
429-438
ISSN
  • 0161-7567 (ISSN-L)
  • 8750-7587
  • 1522-1601
OpenAlex
W2069721298
Cited by
183
References
12
FWCI
4.43
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: AMP-activated protein kinase phosphorylates transcription factors of the CREB family. https://app.cochat.ai/papers/10.1152/japplphysiol.00900.2007
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Thomson, D. M., Herway, S. T., Fillmore, N., Kim, H., Brown, J. D., Barrow, J. R., & Winder, W. W. (2008). AMP-activated protein kinase phosphorylates transcription factors of the CREB family. Journal of Applied Physiology. https://doi.org/10.1152/japplphysiol.00900.2007

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