Tutor, AntonioDelpón Mosquera, María EvaCaballero Collado, RicardoGómez García, RicardoNúñez Fernández, LucíaVaquero González, Luis MiguelTamargo Menéndez, JuanMayor, FedericoPenela, Petronila2024-01-122024-01-122006Tutor AS, Delpón E, Caballero R, Gómez R, Núñez L, Vaquero M, Tamargo J, Mayor F Jr, Penela P. Association of 14-3-3 proteins to beta1-adrenergic receptors modulates Kv11.1 K+ channel activity in recombinant systems. Mol Biol Cell. 2006 Nov;17(11):4666-74. doi: 10.1091/mbc.e06-05-0422.Tutor, Antonio S., et al. «Association of 14-3-3 Proteins to β1 -Adrenergic Receptors Modulates Kv11.1 K+ Channel Activity in Recombinant Systems». Molecular Biology of the Cell, editado por J. Silvio Gutkind, vol. 17, n.o 11, noviembre de 2006, pp. 4666-74. https://doi.org/10.1091/mbc.e06-05-0422.10.1091/mbc.e06-05-0422https://hdl.handle.net/20.500.14352/92791We identify a new mechanism for the beta(1)-adrenergic receptor (beta(1)AR)-mediated regulation of human ether-a-go-go-related gene (HERG) potassium channel (Kv11.1). We find that the previously reported modulatory interaction between Kv11.1 channels and 14-3-3epsilon proteins is competed by wild type beta(1)AR by means of a novel interaction between this receptor and 14-3-3epsilon. The association between beta(1)AR and 14-3-3epsilon is increased by agonist stimulation in both transfected cells and heart tissue and requires cAMP-dependent protein kinase (PKA) activity. The beta(1)AR/14-3-3epsilon association is direct, since it can be recapitulated using purified 14-3-3epsilon and beta(1)AR fusion proteins and is abolished in cells expressing beta(1)AR phosphorylation-deficient mutants. Biochemical and electrophysiological studies of the effects of isoproterenol on Kv11.1 currents recorded using the whole-cell patch clamp demonstrated that beta(1)AR phosphorylation-deficient mutants do not recruit 14-3-3epsilon away from Kv11.1 and display a markedly altered agonist-mediated modulation of Kv11.1 currents compared with wild-type beta(1)AR, increasing instead of inhibiting current amplitudes. Interestingly, such differential modulation is not observed in the presence of 14-3-3 inhibitors. Our results suggest that the dynamic association of 14-3-3 proteins to both beta(1)AR and Kv11.1 channels is involved in the adrenergic modulation of this critical regulator of cardiac repolarization and refractoriness.engjournal article1939-4586https://doi.org/10.1091/mbc.e06-05-0422https://pubmed.ncbi.nlm.nih.gov/16914520/restricted accessBiología molecular (Biología)2415 Biología Molecular