Activation of protein kinase cascades in the heart by hypertrophic G protein-coupled receptor agonists.
Cardiac myocyte hypertrophy involves changes in cell structure and alterations in protein expression regulated at both the transcriptional and translational levels. Hypertrophic G protein-coupled receptor (GPCR) agonists such as endothelin-(ET-1) and phenylephrine stimulate a number of protein kinase cascades in the heart. Mitogen-activated protein kinase (MAPK) cascades stimulated include the extracellularly regulated kinase cascade, the stress-activated protein kinase/c-Jun N-terminal kinase cascade, and the p38 MAPK cascade. All 3 pathways have been implicated in hypertrophy, but recent ex vivo evidence also suggests that there may be additional effects on cell survival. ET-1 and phenylephrine also stimulate the protein kinase B pathway, and this may be involved in the regulation of protein synthesis by these agonists. Thus, protein kinase-mediated signaling may be important in the regulation of the development of myocyte hypertrophy.
Clerk
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Division of Biomedical Sciences, Imperial College School of Medicine, London, United Kingdom.
Sugden
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D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism*; D019332:Endothelin-1 / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000819:agonists*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D014158:Transcription, Genetic
D000316:Adrenergic alpha-Agonists; D019332:Endothelin-1; D011518:Proto-Oncogene Proteins; D010656:Phenylephrine; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins