ArticleBiochemistry2010
Targeting of protein phosphatases PP2A and PP2B to the C-terminus of the L-type calcium channel Ca v1.2.
Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Altered protein homeostasis in cardiovascular diseases contributes to Alzheimer's-like neuropathology.Basic research in cardiology · 2025Article
- Early life seizures chronically disrupt L-type voltage gated calcium channel regulation of mGluR mediated long term depression via interactions with protein phosphatase 2A.Neurobiology of disease · 2025Article
- Synaptic homeostasis transiently leverages Hebbian mechanisms for a multiphasic response to inactivity.Cell reports · 2024Article
- αeLife · 2023Article
- The baseless mutant links protein phosphatase 2A with basal cell identity in the brown alga Ectocarpus.Development (Cambridge, England) · 2023Article
- A Specific microRNA Targets an Elongase of Very Long Chain Fatty Acids to Regulate Fatty Acid Composition and Mitochondrial Morphology of Skeletal Muscle Cells.Animals : an open access journal from MDPI · 2022Article
- Ventricular voltage-gated ion channels: Detection, characteristics, mechanisms, and drug safety evaluation.Clinical and translational medicine · 2021Review
- Post-Translational Modification of Cav1.2 and its Role in Neurodegenerative Diseases.Frontiers in pharmacology · 2021Review
- Involvement of Calcium-Dependent Pathway and β Subunit-Interaction in Neuronal Migration and Callosal Projection Deficits Caused by the Cav1.2 I1166T Mutation in Developing Mouse Neocortex.Frontiers in neuroscience · 2021Article
- βAnnual review of pharmacology and toxicology · 2020Review
- Challenges and Opportunities for Therapeutic Targeting of Calmodulin Kinase II in Heart.Frontiers in pharmacology · 2020Review
- A Review of Cardiovascular Toxicity of Microcystins.Toxins · 2019Review
- Postsynaptic localization and regulation of AMPA receptors and Cav1.2 by β2 adrenergic receptor/PKA and CaThe EMBO journal · 2018Review
- Calmodulin and ATP support activity of the Cav1.2 channel through dynamic interactions with the channel.The Journal of physiology · 2017Article
- Calcium dynamics predict direction of synaptic plasticity in striatal spiny projection neurons.The European journal of neuroscience · 2017Article
- Serine/Threonine Phosphatases in Atrial Fibrillation.Journal of molecular and cellular cardiology · 2017Review
- Roles and regulation of protein phosphatase 2A (PP2A) in the heart.Journal of molecular and cellular cardiology · 2016Review
- Cardiomyocyte specific deletion of PP2A causes cardiac hypertrophy.American journal of translational research · 2016Article
- The PDZ motif of the α1C subunit is not required for surface trafficking and adrenergic modulation of CaV1.2 channel in the heart.The Journal of biological chemistry · 2015Article
- Counteracting Protein Kinase Activity in the Heart: The Multiple Roles of Protein Phosphatases.Frontiers in pharmacology · 2015Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The L-type Ca(2+) channel Ca(v)1.2 forms macromolecular signaling complexes that comprise the β(2) adrenergic receptor, trimeric G(s) protein, adenylyl cyclase, and cAMP-dependent protein kinase (PKA) for efficient signaling in heart and brain. The protein phosphatases PP2A and PP2B are part of this complex. PP2A counteracts increase in Ca(v)1.2 channel activity by PKA and other protein kinases, whereas PP2B can either augment or decrease Ca(v)1.2 currents in cardiomyocytes depending on the precise experimental conditions. We found that PP2A binds to two regions in the C-terminus of the central, pore-forming α(1) subunit of Ca(v)1.2: one region spans residues 1795-1818 and the other residues 1965-1971. PP2B binds immediately downstream of residue 1971. Injection of a peptide that contained residues 1965-1971 and displaced PP2A but not PP2B from endogenous Ca(v)1.2 increased basal and isoproterenol-stimulated L-type Ca(2+) currents in acutely isolated cardiomyocytes. Together with our biochemical data, these physiological results indicate that anchoring of PP2A at this site of Ca(v)1.2 in the heart negatively regulates cardiac L-type currents, likely by counterbalancing basal and stimulated phosphorylation that is mediated by PKA and possibly other kinases.
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Registered trials
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