A-kinase anchoring protein (AKAP)-Lbc-signaling complex mediates α1 adrenergic receptor-induced cardiomyocyte hypertrophy
In response to various pathological stresses, the heart undergoes a pathological remodeling process that is associated with cardiomyocyte hypertrophy. Because cardiac hypertrophy can progress to heart failure, a major cause of lethality worldwide, the intracellular signaling pathways that control ca...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 104; no. 24; pp. 10140 - 10145 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
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National Academy of Sciences
12.06.2007
National Acad Sciences |
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Abstract | In response to various pathological stresses, the heart undergoes a pathological remodeling process that is associated with cardiomyocyte hypertrophy. Because cardiac hypertrophy can progress to heart failure, a major cause of lethality worldwide, the intracellular signaling pathways that control cardiomyocyte growth have been the subject of intensive investigation. It has been known for more than a decade that the small molecular weight GTPase RhoA is involved in the signaling pathways leading to cardiomyocyte hypertrophy. Although some of the hypertrophic pathways activated by RhoA have now been identified, the identity of the exchange factors that modulate its activity in cardiomyocytes is currently unknown. In this study, we show that AKAP-Lbc, an A-kinase anchoring protein (AKAP) with an intrinsic Rho-specific guanine nucleotide exchange factor activity, is critical for activating RhoA and transducing hypertrophic signals downstream of α1-adrenergic receptors (ARs). In particular, our results indicate that suppression of AKAP-Lbc expression by infecting rat neonatal ventricular cardiomyocytes with lentiviruses encoding AKAP-Lbc-specific short hairpin RNAs strongly reduces both α1-AR-mediated RhoA activation and hypertrophic responses. Interestingly, α1-ARs promote AKAP-Lbc activation via a pathway that requires the α subunit of the heterotrimeric G protein G12. These findings identify AKAP-Lbc as the first Rho-guanine nucleotide exchange factor (GEF) involved in the signaling pathways leading to cardiomyocytes hypertrophy. |
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AbstractList | In response to various pathological stresses, the heart undergoes a pathological remodeling process that is associated with cardiomyocyte hypertrophy. Because cardiac hypertrophy can progress to heart failure, a major cause of lethality worldwide, the intracellular signaling pathways that control cardiomyocyte growth have been the subject of intensive investigation. It has been known for more than a decade that the small molecular weight GTPase RhoA is involved in the signaling pathways leading to cardiomyocyte hypertrophy. Although some of the hypertrophic pathways activated by RhoA have now been identified, the identity of the exchange factors that modulate its activity in cardiomyocytes is currently unknown. In this study, we show that AKAP-Lbc, an A-kinase anchoring protein (AKAP) with an intrinsic Rho-specific guanine nucleotide exchange factor activity, is critical for activating RhoA and transducing hypertrophic signals downstream of α1-adrenergic receptors (ARs). In particular, our results indicate that suppression of AKAP-Lbc expression by infecting rat neonatal ventricular cardiomyocytes with lentiviruses encoding AKAP-Lbc-specific short hairpin RNAs strongly reduces both α1-AR-mediated RhoA activation and hypertrophic responses. Interestingly, α1-ARs promote AKAP-Lbc activation via a pathway that requires the α subunit of the heterotrimeric G protein G12. These findings identify AKAP-Lbc as the first Rho-guanine nucleotide exchange factor (GEF) involved in the signaling pathways leading to cardiomyocytes hypertrophy. cardiac hypertrophy Rho GTPase G protein-coupled receptor In response to various pathological stresses, the heart undergoes a pathological remodeling process that is associated with cardiomyocyte hypertrophy. Because cardiac hypertrophy can progress to heart failure, a major cause of lethality worldwide, the intracellular signaling pathways that control cardiomyocyte growth have been the subject of intensive investigation. It has been known for more than a decade that the small molecular weight GTPase RhoA is involved in the signaling pathways leading to cardiomyocyte hypertrophy. Although some of the hypertrophic pathways activated by RhoA have now been identified, the identity of the exchange factors that modulate its activity in cardiomyocytes is currently unknown. In this study, we show that AKAP-Lbc, an A-kinase anchoring protein (AKAP) with an intrinsic Rho-specific guanine nucleotide exchange factor activity, is critical for activating RhoA and transducing hypertrophic signals downstream of α1-adrenergic receptors (ARs). In particular, our results indicate that suppression of AKAP-Lbc expression by infecting rat neonatal ventricular cardiomyocytes with lentiviruses encoding AKAP-Lbc-specific short hairpin RNAs strongly reduces both α1-AR-mediated RhoA activation and hypertrophic responses. Interestingly, α1-ARs promote AKAP-Lbc activation via a pathway that requires the α subunit of the heterotrimeric G protein G12. These findings identify AKAP-Lbc as the first Rho-guanine nucleotide exchange factor (GEF) involved in the signaling pathways leading to cardiomyocytes hypertrophy. In response to various pathological stresses, the heart undergoes a pathological remodeling process that is associated with cardiomyocyte hypertrophy. Because cardiac hypertrophy can progress to heart failure, a major cause of lethality worldwide, the intracellular signaling pathways that control cardiomyocyte growth have been the subject of intensive investigation. It has been known for more than a decade that the small molecular weight GTPase RhoA is involved in the signaling pathways leading to cardiomyocyte hypertrophy. Although some of the hypertrophic pathways activated by RhoA have now been identified, the identity of the exchange factors that modulate its activity in cardiomyocytes is currently unknown. In this study, we show that AKAP-Lbc, an A-kinase anchoring protein (AKAP) with an intrinsic Rho-specific guanine nucleotide exchange factor activity, is critical for activating RhoA and transducing hypertrophic signals downstream of α1-adrenergic receptors (ARs). In particular, our results indicate that suppression of AKAP-Lbc expression by infecting rat neonatal ventricular cardiomyocytes with lentiviruses encoding AKAP-Lbc-specific short hairpin RNAs strongly reduces both α1-AR-mediated RhoA activation and hypertrophic responses. Interestingly, α1-ARs promote AKAP-Lbc activation via a pathway that requires the a subunit of the heterotrimeric G protein G12. These findings identify AKAP-Lbc as the first Rho-guanine nucleotide exchange factor (GEF) involved in the signaling pathways leading to cardiomyocytes hypertrophy. |
Author | Cotecchia, Susanna Pedrazzini, Thierry Diviani, Dario Nenniger-Tosato, Monique Appert-Collin, Aline |
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Cites_doi | 10.1074/jbc.M106629200 10.1126/science.280.5372.2109 10.1161/01.CIR.0000012750.08480.55 10.1093/emboj/16.8.1888 10.1152/ajpheart.2000.278.6.H1769 10.1016/S0092-8674(00)81573-1 10.1074/jbc.M107924200 10.1073/pnas.0234057100 10.1126/science.272.5259.263 10.1074/jbc.271.49.31185 10.1172/JCI200316100 10.1016/S0955-0674(96)80068-8 10.1038/ng1173 10.1074/jbc.274.25.17901 10.1128/MCB.21.5.1463-1474.2001 10.1074/jbc.274.9.5868 10.1101/gad.915701 10.1128/MCB.22.12.4053-4061.2002 10.1016/j.molcel.2004.09.015 10.1128/MCB.24.19.8374-8385.2004 10.1161/01.CIR.0000120390.68287.BB 10.1073/pnas.91.21.10109 10.1074/jbc.M414440200 10.1074/jbc.C400105200 10.1242/jcs.115.3.629 10.1083/jcb.200102110 10.1074/jbc.M411322200 10.1038/sj.emboj.7600287 10.1172/JCI118166 10.1161/01.RES.0000043282.39776.7C 10.1038/nrm1527 10.1073/pnas.95.17.10140 10.1074/jbc.M409710200 |
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Snippet | In response to various pathological stresses, the heart undergoes a pathological remodeling process that is associated with cardiomyocyte hypertrophy. Because... |
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SubjectTerms | Antibodies Biological Sciences Hypertrophy Infections Messenger RNA Myocardium Polymerase chain reaction Rats Receptors RNA Viruses |
Title | A-kinase anchoring protein (AKAP)-Lbc-signaling complex mediates α1 adrenergic receptor-induced cardiomyocyte hypertrophy |
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