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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
48
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pubmed:dateCreated |
2006-11-27
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pubmed:abstractText |
The AMP-activated protein kinase (AMPK) and cAMP signaling systems are both key regulators of cellular metabolism. In this study, we show that AMPK activity is attenuated in response to cAMP-elevating agents through modulation of at least two of its alpha subunit phosphorylation sites, viz. alpha-Thr(172) and alpha1-Ser(485)/alpha2-Ser(491), in the clonal beta-cell line INS-1 as well as in mouse embryonic fibroblasts and COS cells. Forskolin, isobutylmethylxanthine, and the glucose-dependent insulinotropic peptide inhibited AMPK activity and reduced phosphorylation of the activation loop alpha-Thr(172) via inhibition of calcium/calmodulin-dependent protein kinase kinase-alpha and -beta, but not LKB1. These agents also enhanced phosphorylation of alpha-Ser(485/491) by the cAMP-dependent protein kinase. AMPK alpha-Ser(485/491) phosphorylation was necessary but not sufficient for inhibition of AMPK activity in response to forskolin/isobutylmethylxanthine. We show that AMPK alpha-Ser(485/491) can be a site for autophosphorylation, which may play a role in limiting AMPK activation in response to energy depletion or other regulators. Thus, our findings not only demonstrate cross-talk between the cAMP/cAMP-dependent protein kinase and AMPK signaling modules, but also describe a novel mechanism by which multisite phosphorylation of AMPK contributes to regulation of its enzyme activity.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-Methyl-3-isobutylxanthine,
http://linkedlifedata.com/resource/pubmed/chemical/AMP-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Camkk1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphodiesterase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
281
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
36662-72
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:17023420-1-Methyl-3-isobutylxanthine,
pubmed-meshheading:17023420-AMP-Activated Protein Kinases,
pubmed-meshheading:17023420-Animals,
pubmed-meshheading:17023420-COS Cells,
pubmed-meshheading:17023420-Calcium-Calmodulin-Dependent Protein Kinase Kinase,
pubmed-meshheading:17023420-Cercopithecus aethiops,
pubmed-meshheading:17023420-Cyclic AMP,
pubmed-meshheading:17023420-Forskolin,
pubmed-meshheading:17023420-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:17023420-Glucose,
pubmed-meshheading:17023420-Mice,
pubmed-meshheading:17023420-Multienzyme Complexes,
pubmed-meshheading:17023420-Peptides,
pubmed-meshheading:17023420-Phosphodiesterase Inhibitors,
pubmed-meshheading:17023420-Phosphorylation,
pubmed-meshheading:17023420-Protein-Serine-Threonine Kinases,
pubmed-meshheading:17023420-Rats
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pubmed:year |
2006
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pubmed:articleTitle |
Regulation of AMP-activated protein kinase by multisite phosphorylation in response to agents that elevate cellular cAMP.
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pubmed:affiliation |
Department of Medicine and Biochemistry, Dartmouth Medical School, Remsen 322, N. College St., Hanover, NH 03755, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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