AMPK antagonizes hepatic glucagon-stimulated cyclic AMP signalling via phosphorylation-induced activation of cyclic nucleotide phosphodiesterase 4B

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AMPK antagonizes hepatic glucagon-stimulated cyclic AMP signalling via phosphorylation-induced activation of cyclic nucleotide phosphodiesterase 4B. / Johanns, M.; Lai, Y. C.; Hsu, M. F.; Jacobs, R.; Vertommen, D.; Van Sande, J.; Dumont, J. E.; Woods, A.; Carling, D.; Hue, L.; Viollet, B.; Foretz, M.; Rider, M. H.

In: Nature Communications, Vol. 7, 10856, 08.03.2016.

Research output: Contribution to journalArticle

Harvard

Johanns, M, Lai, YC, Hsu, MF, Jacobs, R, Vertommen, D, Van Sande, J, Dumont, JE, Woods, A, Carling, D, Hue, L, Viollet, B, Foretz, M & Rider, MH 2016, 'AMPK antagonizes hepatic glucagon-stimulated cyclic AMP signalling via phosphorylation-induced activation of cyclic nucleotide phosphodiesterase 4B', Nature Communications, vol. 7, 10856. https://doi.org/10.1038/ncomms10856

APA

Johanns, M., Lai, Y. C., Hsu, M. F., Jacobs, R., Vertommen, D., Van Sande, J., Dumont, J. E., Woods, A., Carling, D., Hue, L., Viollet, B., Foretz, M., & Rider, M. H. (2016). AMPK antagonizes hepatic glucagon-stimulated cyclic AMP signalling via phosphorylation-induced activation of cyclic nucleotide phosphodiesterase 4B. Nature Communications, 7, [10856]. https://doi.org/10.1038/ncomms10856

Vancouver

Author

Johanns, M. ; Lai, Y. C. ; Hsu, M. F. ; Jacobs, R. ; Vertommen, D. ; Van Sande, J. ; Dumont, J. E. ; Woods, A. ; Carling, D. ; Hue, L. ; Viollet, B. ; Foretz, M. ; Rider, M. H. / AMPK antagonizes hepatic glucagon-stimulated cyclic AMP signalling via phosphorylation-induced activation of cyclic nucleotide phosphodiesterase 4B. In: Nature Communications. 2016 ; Vol. 7.

Bibtex

@article{61352a2b60a74524a454692ee0b09bfa,
title = "AMPK antagonizes hepatic glucagon-stimulated cyclic AMP signalling via phosphorylation-induced activation of cyclic nucleotide phosphodiesterase 4B",
abstract = "Biguanides such as metformin have previously been shown to antagonize hepatic glucagon-stimulated cyclic AMP (cAMP) signalling independently of AMP-activated protein kinase (AMPK) via direct inhibition of adenylate cyclase by AMP. Here we show that incubation of hepatocytes with the small-molecule AMPK activator 991 decreases glucagon-stimulated cAMP accumulation, cAMP-dependent protein kinase (PKA) activity and downstream PKA target phosphorylation. Moreover, incubation of hepatocytes with 991 increases the Vmax of cyclic nucleotide phosphodiesterase 4B (PDE4B) without affecting intracellular adenine nucleotide concentrations. The effects of 991 to decrease glucagon-stimulated cAMP concentrations and activate PDE4B are lost in hepatocytes deleted for both catalytic subunits of AMPK. PDE4B is phosphorylated by AMPK at three sites, and by site-directed mutagenesis, Ser304 phosphorylation is important for activation. In conclusion, we provide a new mechanism by which AMPK antagonizes hepatic glucagon signalling via phosphorylation-induced PDE4B activation.",
keywords = "Cell Signalling, Kinases, Medical research, Phosphorylation",
author = "M. Johanns and Lai, {Y. C.} and Hsu, {M. F.} and R. Jacobs and D. Vertommen and {Van Sande}, J. and Dumont, {J. E.} and A. Woods and D. Carling and L. Hue and B. Viollet and M. Foretz and Rider, {M. H.}",
year = "2016",
month = mar,
day = "8",
doi = "10.1038/ncomms10856",
language = "English",
volume = "7",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Springer",

}

RIS

TY - JOUR

T1 - AMPK antagonizes hepatic glucagon-stimulated cyclic AMP signalling via phosphorylation-induced activation of cyclic nucleotide phosphodiesterase 4B

AU - Johanns, M.

AU - Lai, Y. C.

AU - Hsu, M. F.

AU - Jacobs, R.

AU - Vertommen, D.

AU - Van Sande, J.

AU - Dumont, J. E.

AU - Woods, A.

AU - Carling, D.

AU - Hue, L.

AU - Viollet, B.

AU - Foretz, M.

AU - Rider, M. H.

PY - 2016/3/8

Y1 - 2016/3/8

N2 - Biguanides such as metformin have previously been shown to antagonize hepatic glucagon-stimulated cyclic AMP (cAMP) signalling independently of AMP-activated protein kinase (AMPK) via direct inhibition of adenylate cyclase by AMP. Here we show that incubation of hepatocytes with the small-molecule AMPK activator 991 decreases glucagon-stimulated cAMP accumulation, cAMP-dependent protein kinase (PKA) activity and downstream PKA target phosphorylation. Moreover, incubation of hepatocytes with 991 increases the Vmax of cyclic nucleotide phosphodiesterase 4B (PDE4B) without affecting intracellular adenine nucleotide concentrations. The effects of 991 to decrease glucagon-stimulated cAMP concentrations and activate PDE4B are lost in hepatocytes deleted for both catalytic subunits of AMPK. PDE4B is phosphorylated by AMPK at three sites, and by site-directed mutagenesis, Ser304 phosphorylation is important for activation. In conclusion, we provide a new mechanism by which AMPK antagonizes hepatic glucagon signalling via phosphorylation-induced PDE4B activation.

AB - Biguanides such as metformin have previously been shown to antagonize hepatic glucagon-stimulated cyclic AMP (cAMP) signalling independently of AMP-activated protein kinase (AMPK) via direct inhibition of adenylate cyclase by AMP. Here we show that incubation of hepatocytes with the small-molecule AMPK activator 991 decreases glucagon-stimulated cAMP accumulation, cAMP-dependent protein kinase (PKA) activity and downstream PKA target phosphorylation. Moreover, incubation of hepatocytes with 991 increases the Vmax of cyclic nucleotide phosphodiesterase 4B (PDE4B) without affecting intracellular adenine nucleotide concentrations. The effects of 991 to decrease glucagon-stimulated cAMP concentrations and activate PDE4B are lost in hepatocytes deleted for both catalytic subunits of AMPK. PDE4B is phosphorylated by AMPK at three sites, and by site-directed mutagenesis, Ser304 phosphorylation is important for activation. In conclusion, we provide a new mechanism by which AMPK antagonizes hepatic glucagon signalling via phosphorylation-induced PDE4B activation.

KW - Cell Signalling

KW - Kinases

KW - Medical research

KW - Phosphorylation

UR - http://www.scopus.com/inward/record.url?scp=84960427343&partnerID=8YFLogxK

U2 - 10.1038/ncomms10856

DO - 10.1038/ncomms10856

M3 - Article

C2 - 26952277

AN - SCOPUS:84960427343

VL - 7

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 10856

ER -