A-kinase-anchoring protein-Lbc anchors IκB kinase β to support interleukin-6-mediated cardiomyocyte hypertrophy
| Autor: | Susanna Cotecchia, Cosmo D. del Vescovo, Dario Diviani |
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| Rok vydání: | 2012 |
| Předmět: |
A-kinase-anchoring protein
medicine.medical_specialty A Kinase Anchor Proteins IκB kinase Biology Muscle hypertrophy Proinflammatory cytokine Minor Histocompatibility Antigens Rats Sprague-Dawley Mice Internal medicine Proto-Oncogene Proteins Receptors Adrenergic alpha-1 medicine Animals Guanine Nucleotide Exchange Factors Humans Myocytes Cardiac Molecular Biology rho-Associated Kinases Interleukin-6 I-Kappa-B Kinase NF-kappa B Gene Expression Regulation Developmental Articles Cell Biology Hypertrophy NFKB1 Recombinant Proteins Cell biology I-kappa B Kinase Rats Endocrinology Mutation Commentary Signal transduction rhoA GTP-Binding Protein Signal Transduction |
| Zdroj: | Molecular and cellular biology. 33(1) |
| ISSN: | 1098-5549 |
| Popis: | In response to stress, the heart undergoes a pathological remodeling process associated with hypertrophy and the reexpression of a fetal gene program that ultimately causes cardiac dysfunction and heart failure. In this study, we show that A-kinase-anchoring protein (AKAP)–Lbc and the inhibitor of NF-κB kinase subunit β (IKKβ) form a transduction complex in cardiomyocytes that controls the production of proinflammatory cytokines mediating cardiomyocyte hypertrophy. In particular, we can show that activation of IKKβ within the AKAP-Lbc complex promotes NF-κB-dependent production of interleukin-6 (IL-6), which in turn enhances fetal gene expression and cardiomyocyte growth. These findings provide a new mechanistic hypothesis explaining how hypertrophic signals are coordinated and conveyed to interleukin-mediated transcriptional reprogramming events in cardiomyocytes. |
| Databáze: | OpenAIRE |
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