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EMBO J
2004 Jun 02;2311:2196-205. doi: 10.1038/sj.emboj.7600228.
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Assembly of a Ca2+-dependent BK channel signaling complex by binding to beta2 adrenergic receptor.
Liu G, Shi J, Yang L, Cao L, Park SM, Cui J, Marx SO.
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Large-conductance voltage and Ca2+-activated potassium channels (BKCa) play a critical role in modulating contractile tone of smooth muscle, and neuronal processes. In most mammalian tissues, activation of beta-adrenergic receptors and protein kinase A (PKAc) increases BKCa channel activity, contributing to sympathetic nervous system/hormonal regulation of membrane excitability. Here we report the requirement of an association of the beta2-adrenergic receptor (beta2AR) with the pore forming alpha subunit of BKCa and an A-kinase-anchoring protein (AKAP79/150) for beta2 agonist regulation. beta2AR can simultaneously interact with both BKCa and L-type Ca2+ channels (Cav1.2) in vivo, which enables the assembly of a unique, highly localized signal transduction complex to mediate Ca2+- and phosphorylation-dependent modulation of BKCa current. Our findings reveal a novel function for G protein-coupled receptors as a scaffold to couple two families of ion channels into a physical and functional signaling complex to modulate beta-adrenergic regulation of membrane excitability.
Alioua,
The large conductance, voltage-dependent, and calcium-sensitive K+ channel, Hslo, is a target of cGMP-dependent protein kinase phosphorylation in vivo.
1998, Pubmed,
Xenbase
Alioua,
The large conductance, voltage-dependent, and calcium-sensitive K+ channel, Hslo, is a target of cGMP-dependent protein kinase phosphorylation in vivo.
1998,
Pubmed
,
Xenbase Angers,
Detection of beta 2-adrenergic receptor dimerization in living cells using bioluminescence resonance energy transfer (BRET).
2000,
Pubmed Barki-Harrington,
Dual inhibition of beta-adrenergic and angiotensin II receptors by a single antagonist: a functional role for receptor-receptor interaction in vivo.
2003,
Pubmed Barman,
cAMP activates BKCa channels in pulmonary arterial smooth muscle via cGMP-dependent protein kinase.
2003,
Pubmed Bar-Sinai,
The GppNHp-activated adenylyl cyclase complex from turkey erythrocyte membranes can be isolated with its beta gamma subunits.
1992,
Pubmed Brenner,
Vasoregulation by the beta1 subunit of the calcium-activated potassium channel.
2000,
Pubmed Butler,
mSlo, a complex mouse gene encoding "maxi" calcium-activated potassium channels.
1993,
Pubmed
,
Xenbase Carl,
Regulation of Ca(2+)-activated K+ channels by protein kinase A and phosphatase inhibitors.
1991,
Pubmed Chen-Izu,
G(i)-dependent localization of beta(2)-adrenergic receptor signaling to L-type Ca(2+) channels.
2000,
Pubmed Chung,
Protein kinase activity closely associated with a reconstituted calcium-activated potassium channel.
1991,
Pubmed Cong,
Regulation of membrane targeting of the G protein-coupled receptor kinase 2 by protein kinase A and its anchoring protein AKAP79.
2001,
Pubmed Davare,
A beta2 adrenergic receptor signaling complex assembled with the Ca2+ channel Cav1.2.
2001,
Pubmed Esguerra,
Cloned Ca(2+)-dependent K+ channel modulated by a functionally associated protein kinase.
1994,
Pubmed
,
Xenbase Faux,
Mechanism of A-kinase-anchoring protein 79 (AKAP79) and protein kinase C interaction.
1999,
Pubmed Fraser,
Assembly of an A kinase-anchoring protein-beta(2)-adrenergic receptor complex facilitates receptor phosphorylation and signaling.
2000,
Pubmed Fury,
Molecular BKology: the study of splicing and dicing.
2002,
Pubmed Gao,
Identification and subcellular localization of the subunits of L-type calcium channels and adenylyl cyclase in cardiac myocytes.
1997,
Pubmed Gola,
Colocalization of active KCa channels and Ca2+ channels within Ca2+ domains in helix neurons.
1993,
Pubmed Green,
A proline-rich region of the third intracellular loop imparts phenotypic beta 1-versus beta 2-adrenergic receptor coupling and sequestration.
1994,
Pubmed Guia,
Local Ca2+ entry through L-type Ca2+ channels activates Ca2+-dependent K+ channels in rabbit coronary myocytes.
1999,
Pubmed Hall,
The beta2-adrenergic receptor interacts with the Na+/H+-exchanger regulatory factor to control Na+/H+ exchange.
1998,
Pubmed Herrera,
Differential regulation of SK and BK channels by Ca(2+) signals from Ca(2+) channels and ryanodine receptors in guinea-pig urinary bladder myocytes.
2002,
Pubmed Hulme,
A novel leucine zipper targets AKAP15 and cyclic AMP-dependent protein kinase to the C terminus of the skeletal muscle Ca2+ channel and modulates its function.
2002,
Pubmed Hulme,
Beta-adrenergic regulation requires direct anchoring of PKA to cardiac CaV1.2 channels via a leucine zipper interaction with A kinase-anchoring protein 15.
2003,
Pubmed Joiner,
Formation of intermediate-conductance calcium-activated potassium channels by interaction of Slack and Slo subunits.
1998,
Pubmed Klauck,
Coordination of three signaling enzymes by AKAP79, a mammalian scaffold protein.
1996,
Pubmed Knaus,
Distribution of high-conductance Ca(2+)-activated K+ channels in rat brain: targeting to axons and nerve terminals.
1996,
Pubmed Kume,
Stimulatory and inhibitory regulation of calcium-activated potassium channels by guanine nucleotide-binding proteins.
1992,
Pubmed Kume,
Regulation of Ca2+-dependent K+-channel activity in tracheal myocytes by phosphorylation.
1989,
Pubmed Lagrutta,
Functional differences among alternatively spliced variants of Slowpoke, a Drosophila calcium-activated potassium channel.
1994,
Pubmed Lancaster,
Calcium activates two types of potassium channels in rat hippocampal neurons in culture.
1991,
Pubmed Marrion,
Selective activation of Ca2+-activated K+ channels by co-localized Ca2+ channels in hippocampal neurons.
1998,
Pubmed Marx,
Phosphorylation-dependent regulation of ryanodine receptors: a novel role for leucine/isoleucine zippers.
2001,
Pubmed Marx,
Requirement of a macromolecular signaling complex for beta adrenergic receptor modulation of the KCNQ1-KCNE1 potassium channel.
2002,
Pubmed Marx,
PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts.
2000,
Pubmed Minami,
Protein kinase C inhibits the Ca(2+)-activated K+ channel of cultured porcine coronary artery smooth muscle cells.
1993,
Pubmed Nara,
Reconstitution of beta-adrenergic modulation of large conductance, calcium-activated potassium (maxi-K) channels in Xenopus oocytes. Identification of the camp-dependent protein kinase phosphorylation site.
1998,
Pubmed
,
Xenbase Nelson,
Relaxation of arterial smooth muscle by calcium sparks.
1995,
Pubmed Pawson,
Signaling through scaffold, anchoring, and adaptor proteins.
1997,
Pubmed Pelaia,
Potential role of potassium channel openers in the treatment of asthma and chronic obstructive pulmonary disease.
2002,
Pubmed Pineda,
Specificity in the interaction of HVA Ca2+ channel types with Ca2+-dependent AHPs and firing behavior in neocortical pyramidal neurons.
1998,
Pubmed Reinhart,
Kinase and phosphatase activities intimately associated with a reconstituted calcium-dependent potassium channel.
1995,
Pubmed Reinhart,
Modulation of calcium-activated potassium channels from rat brain by protein kinase A and phosphatase 2A.
1991,
Pubmed Roberts,
Colocalization of ion channels involved in frequency selectivity and synaptic transmission at presynaptic active zones of hair cells.
1990,
Pubmed Robitaille,
Functional colocalization of calcium and calcium-gated potassium channels in control of transmitter release.
1993,
Pubmed Rockman,
Seven-transmembrane-spanning receptors and heart function.
2002,
Pubmed Sadoshima,
Cyclic AMP modulates Ca-activated K channel in cultured smooth muscle cells of rat aortas.
1988,
Pubmed Salahpour,
Biochemical characterization of beta2-adrenergic receptor dimers and oligomers.
2003,
Pubmed Sansom,
Regulation of large calcium-activated potassium channels by protein phosphatase 2A.
1997,
Pubmed Schubert,
Protein kinases: tuners of the BKCa channel in smooth muscle.
2001,
Pubmed Schubert,
cAMP-dependent protein kinase is in an active state in rat small arteries possessing a myogenic tone.
1999,
Pubmed Shih,
Dynamic complexes of beta2-adrenergic receptors with protein kinases and phosphatases and the role of gravin.
1999,
Pubmed Storm,
Action potential repolarization and a fast after-hyperpolarization in rat hippocampal pyramidal cells.
1987,
Pubmed Sun,
Calcium influx via L- and N-type calcium channels activates a transient large-conductance Ca2+-activated K+ current in mouse neocortical pyramidal neurons.
2003,
Pubmed Tao,
Protein kinase A regulates AKAP250 (gravin) scaffold binding to the beta2-adrenergic receptor.
2003,
Pubmed Tian,
Alternative splicing switches potassium channel sensitivity to protein phosphorylation.
2001,
Pubmed Tian,
Leucine zipper domain targets cAMP-dependent protein kinase to mammalian BK channels.
2003,
Pubmed Wallner,
Characterization of and modulation by a beta-subunit of a human maxi KCa channel cloned from myometrium.
1995,
Pubmed
,
Xenbase Wang,
Simultaneous binding of two protein kinases to a calcium-dependent potassium channel.
1999,
Pubmed White,
cAMP-dependent vasodilators cross-activate the cGMP-dependent protein kinase to stimulate BK(Ca) channel activity in coronary artery smooth muscle cells.
2000,
Pubmed Widmer,
Conditional protein phosphorylation regulates BK channel activity in rat cerebellar Purkinje neurons.
2003,
Pubmed Xiao,
Beta-adrenergic signaling in the heart: dual coupling of the beta2-adrenergic receptor to G(s) and G(i) proteins.
2001,
Pubmed Zhou,
Modulation of Drosophila slowpoke calcium-dependent potassium channel activity by bound protein kinase a catalytic subunit.
2002,
Pubmed Zhou,
Spontaneous activation of beta(2)- but not beta(1)-adrenoceptors expressed in cardiac myocytes from beta(1)beta(2) double knockout mice.
2000,
Pubmed Zhou,
A molecular switch for specific stimulation of the BKCa channel by cGMP and cAMP kinase.
2001,
Pubmed
