Source:http://linkedlifedata.com/resource/pubmed/id/19060905
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2009-1-8
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| pubmed:abstractText |
The extracellular-regulated kinases ERK1 and ERK2 (commonly referred to as ERK1/2) have a crucial role in cardiac hypertrophy. ERK1/2 is activated by mitogen-activated protein kinase kinase-1 (MEK1) and MEK2 (commonly referred to as MEK1/2)-dependent phosphorylation in the TEY motif of the activation loop, but how ERK1/2 is targeted toward specific substrates is not well understood. Here we show that autophosphorylation of ERK1/2 on Thr188 directs ERK1/2 to phosphorylate nuclear targets known to cause cardiac hypertrophy. Thr188 autophosphorylation requires the activation and assembly of the entire Raf-MEK-ERK kinase cascade, phosphorylation of the TEY motif, dimerization of ERK1/2 and binding to G protein betagamma subunits released from activated G(q). Thr188 phosphorylation of ERK1/2 was observed in isolated cardiomyocytes induced to undergo hypertrophic growth, in mice upon stimulation of G(q)-coupled receptors or after aortic banding and in failing human hearts. Experiments using transgenic mouse models carrying mutations at the Thr188 phosphorylation site of ERK2 suggested a causal relationship to cardiac hypertrophy. We propose that specific phosphorylation events on ERK1/2 integrate differing upstream signals (Raf1-MEK1/2 or G protein-coupled receptor-G(q)) to induce cardiac hypertrophy.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein beta Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein gamma Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Threonine
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
1546-170X
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
15
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
75-83
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:19060905-Amino Acid Substitution,
pubmed-meshheading:19060905-Animals,
pubmed-meshheading:19060905-COS Cells,
pubmed-meshheading:19060905-Cardiomegaly,
pubmed-meshheading:19060905-Cells, Cultured,
pubmed-meshheading:19060905-Cercopithecus aethiops,
pubmed-meshheading:19060905-GTP-Binding Protein beta Subunits,
pubmed-meshheading:19060905-GTP-Binding Protein gamma Subunits,
pubmed-meshheading:19060905-Heart Failure,
pubmed-meshheading:19060905-Humans,
pubmed-meshheading:19060905-MAP Kinase Signaling System,
pubmed-meshheading:19060905-Mice,
pubmed-meshheading:19060905-Mice, Transgenic,
pubmed-meshheading:19060905-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:19060905-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:19060905-Models, Biological,
pubmed-meshheading:19060905-Phosphorylation,
pubmed-meshheading:19060905-Protein Binding,
pubmed-meshheading:19060905-Protein Multimerization,
pubmed-meshheading:19060905-Signal Transduction,
pubmed-meshheading:19060905-Threonine
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| pubmed:year |
2009
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| pubmed:articleTitle |
A new type of ERK1/2 autophosphorylation causes cardiac hypertrophy.
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| pubmed:affiliation |
Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Strasse 9, Würzburg, Germany. lorenz@toxi.uni-wuerzburg.de
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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