title: A-kinase-anchoring protein-Lbc anchors IκB kinase β to support interleukin-6-mediated cardiomyocyte hypertrophy.
abstract: 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.
authors.affiliation: Département de Pharmacologie et de Toxicologie, University of Lausanne, Lausanne, Switzerland.
authors.forename: Cosmo Damiano
authors.initials: CD
authors.lastname: del Vescovo
authors.forename: Susanna
authors.initials: S
authors.lastname: Cotecchia
authors.forename: Dario
authors.initials: D
authors.lastname: Diviani
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018507:Gene Expression Regulation, Developmental; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006984:Hypertrophy / Q000378:metabolism; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D051379:Mice; D015778:Minor Histocompatibility Antigens; D009154:Mutation; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D054758:A Kinase Anchor Proteins; C085467:AKAP13 protein, human; C526201:Akap13 protein, mouse; D020662:Guanine Nucleotide Exchange Factors; D015850:Interleukin-6; D015778:Minor Histocompatibility Antigens; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D018340:Receptors, Adrenergic, alpha-1; D011994:Recombinant Proteins; D054460:rho-Associated Kinases; D051550:I-kappa B Kinase; D020742:rhoA GTP-Binding Protein