ArticleThe Journal of general physiology2014
Differential regulation of CaV1.2 channels by cAMP-dependent protein kinase bound to A-kinase anchoring proteins 15 and 79/150.
Article in The Journal of general physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 33 citations in OpenAlex.
- Phosphodiesterase 8 regulation of excitation-contraction coupling as a target for cardiovascular disease: is it my turn now?American journal of physiology. Heart and circulatory physiology · 2026Review
- Subcellular Organization of the cAMP Signaling Pathway.Pharmacological reviews · 2021Review
- α-Actinin-1 promotes activity of the L-type CaThe EMBO journal · 2020Article
- The Ion Channel and GPCR Toolkit of Brain Capillary Pericytes.Frontiers in cellular neuroscience · 2020Review
- The AKAP Cypher/Zasp contributes to β-adrenergic/PKA stimulation of cardiac CaThe Journal of general physiology · 2018Article
- Identification of a novel cAMP dependent protein kinase A phosphorylation site on the human cardiac calcium channel.Scientific reports · 2017Article
- Protein kinase A regulates C-terminally truncated CaThe Journal of physiology · 2017Article
- Calcineurin signaling in the heart: The importance of time and place.Journal of molecular and cellular cardiology · 2017Review
- Phosphorylation of Ser1928 mediates the enhanced activity of the L-type Ca2+ channel Cav1.2 by the β2-adrenergic receptor in neurons.Science signaling · 2017Article
- Cannabinoid signalling inhibits sarcoplasmic CaThe Journal of physiology · 2016Article
- Drosophila SLC5A11 Mediates Hunger by Regulating K(+) Channel Activity.Current biology : CB · 2016Article
- Phosphorylation of Cav1.2 on S1928 uncouples the L-type Ca2+ channel from the β2 adrenergic receptor.The EMBO journal · 2016Article
- FRET biosensors reveal AKAP-mediated shaping of subcellular PKA activity and a novel mode of Ca(2+)/PKA crosstalk.Cellular signalling · 2016Article
- Mechanisms and dynamics of AKAP79/150-orchestrated multi-protein signalling complexes in brain and peripheral nerve.The Journal of physiology · 2016Review
- Phosphorylation of the Cav3.2 T-type calcium channel directly regulates its gating properties.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Regulation of Cardiac Calcium Channels in the Fight-or-Flight Response.Current molecular pharmacology · 2015Review
- More than a pore: ion channel signaling complexes.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Review
- Of ATP receptors, opioid receptors, and AKAP regulation of calcium channels.The Journal of general physiology · 2014Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
The CaV1.1 and CaV1.2 voltage-gated calcium channels initiate excitation-contraction coupling in skeletal and cardiac myocytes, excitation-transcription coupling in neurons, and many other cellular processes. Up-regulation of their activity by the β-adrenergic-PKA signaling pathway increases these physiological responses. PKA up-regulation of CaV1.2 activity can be reconstituted in a transfected cell system expressing CaV1.2Δ1800 truncated at the in vivo proteolytic processing site, the distal C-terminal domain (DCT; CaV1.2[1801-2122]), the auxiliary α2δ and β subunits of CaV1.2 channels, and A-kinase anchoring protein-15 (AKAP15), which binds to a site in the DCT. AKAP79/150 binds to the same site in the DCT as AKAP15. Here we report that AKAP79 is ineffective in supporting up-regulation of CaV1.2 channel activity by PKA, even though it binds to the same site in the DCT and inhibits the up-regulation of CaV1.2 channel activity supported by AKAP15. Mutation of the calcineurin-binding site in AKAP79 (AKAP79ΔPIX) allows it to support PKA-dependent up-regulation of CaV1.2 channel activity, suggesting that calcineurin bound to AKAP79 rapidly dephosphorylates CaV1.2 channels, thereby preventing their regulation by PKA. Both AKAP15 and AKAP79ΔPIX exert their regulatory effects on CaV1.2 channels in transfected cells by interaction with the modified leucine zipper motif in the DCT. Our results introduce an unexpected mode of differential regulation by AKAPs, in which binding of different AKAPs at a single site can competitively confer differential regulatory effects on the target protein by their association with different signaling proteins.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.