ArticleProceedings of the National Academy of Sciences of the United States of America2007
Protein kinase A activates protein phosphatase 2A by phosphorylation of the B56delta subunit.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers, 1 of them a synthesis that pooled it.
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Who cites it
153 citing papers in PubMed, 1 synthesis or guideline pooled it, 257 citations in OpenAlex.
- The Signaling and Pharmacology of the Dopamine D1 Receptor.Frontiers in cellular neuroscience · 2021Pooled it
- Protein phosphatase 2A is regulated by protein kinase Cα (PKCα)-dependent phosphorylation of its targeting subunit B56α at Ser41.The Journal of biological chemistry · 2014Trial
- Low Brain Levels of Dietary Polyphenols and Their Conjugates: Reassessing Mechanisms of Alzheimer's Disease Prevention.Journal of dementia and alzheimer's disease · 2026Article
- Early-onset Parkinsonism and cognitive delay: think about PPP2R5D.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- Intercellular cyclic nucleotide dynamics mediate oocyte meiosis in mammalian preovulatory follicles.Current topics in developmental biology · 2026Review
- Sleep prevents brain phosphoproteome disruption to safeguard survival.Cell discovery · 2025Article
- Phosphatases Control the Duration and Range of cAMP/PKA Microdomains.Function (Oxford, England) · 2025Article
- A de novo missense mutation in PPP2R5D alters dopamine pathways and morphology of iPSC-derived midbrain neurons.Stem cells (Dayton, Ohio) · 2025Article
- Enhanced kinase translocation reporters for simultaneous real-time measurement of PKA, ERK, and CabioRxiv : the preprint server for biology · 2024Article
- Emerging Roles of B56 Phosphorylation and Binding Motif in PP2A-B56 Holoenzyme Biological Function.International journal of molecular sciences · 2024Review
- Phosphatases modified by LH signaling in ovarian follicles: testing their role in regulating the NPR2 guanylyl cyclase†.Biology of reproduction · 2024Article
- B56δ long-disordered arms form a dynamic PP2A regulation interface coupled with global allostery and Jordan's syndrome mutations.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Slik maintains tissue homeostasis by preventing JNK-mediated apoptosis.Cell division · 2023Article
- Phosphatases modified by LH signaling in ovarian follicles: testing their role in regulating the NPR2 guanylyl cyclase.bioRxiv : the preprint server for biology · 2023Article
- Protein Phosphatase 2A as a Therapeutic Target in Pulmonary Diseases.Medicina (Kaunas, Lithuania) · 2023Review
- Numerous Trigger-like Interactions of Kinases/Protein Phosphatases in Human Skeletal Muscles Can Underlie Transient Processes in Activation of Signaling Pathways during Exercise.International journal of molecular sciences · 2023Review
- Disease mutations and phosphorylation alter the allosteric pathways involved in autoinhibition of protein phosphatase 2A.The Journal of chemical physics · 2023Article
- Extended regulation interface coupled to the allosteric network and disease mutations in the PP2A-B56δ holoenzyme.bioRxiv : the preprint server for biology · 2023Article
- Forebrain-specific conditional calcineurin deficiency induces dentate gyrus immaturity and hyper-dopaminergic signaling in mice.Molecular brain · 2022Article
- LCK-Mediated RIPK3 Activation Controls Double-Positive Thymocyte Proliferation and Restrains Thymic Lymphoma by Regulating the PP2A-ERK Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
93 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Our previous studies of DARPP-32 in striatal slices have shown that activation of D1 receptors leads to cAMP-dependent dephosphorylation of Thr-75, the Cdk5 site in DARPP-32. In the current study, we have elucidated a mechanism whereby protein phosphatase 2A (PP2A) is activated by a cAMP/PKA-dependent pathway, leading to dephosphorylation of Thr-75. PP2A consists of a catalytic C subunit that associates with the scaffolding A subunit and a variety of B subunits. We have found that the A/C subunits of PP2A, in association with the B56delta (or PPP2R5D) regulatory subunit, is an active DARPP-32 phosphatase. The B56delta subunit expressed in HEK293 cells forms a heterotrimeric assembly that catalyzes PKA-mediated dephosphorylation at Thr-75 in DARPP-32 (also cotransfected into HEK293 cells). The B56delta subunit is phosphorylated by PKA, and this increases the overall activity of PP2A in vitro and in vivo. Among four PKA-phosphorylation sites identified in B56delta in vitro, Ser-566 was found to be critical for the regulation of PP2A activity. Moreover, Ser-566 was phosphorylated by PKA in response to activation of D1 receptors in striatal slices. Based on these studies, we propose that the B56delta/A/C PP2A complex regulates the dephosphorylation of DARPP-32 at Thr-75, thereby helping coordinate the efficacy of dopaminergic neurotransmission in striatal neurons. Moreover, stimulation of protein phosphatase activity by this mechanism may represent an important signaling pathway regulated by cAMP in neurons and other types of cell.
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