ArticleMolecular cell2011
Inhibition of protein phosphatase 2A activity by PI3Kγ regulates β-adrenergic receptor function.
Article in Molecular cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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The trial behind it
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Who cites it
58 citing papers in PubMed, 89 citations in OpenAlex.
- Gut Microbiota-Generated Phenylacetylglutamine and Heart Failure.Circulation. Heart failure · 2023Trial
- Gut microbe-generated phenylacetylglutamine is an endogenous allosteric modulator of β2-adrenergic receptors.Nature communications · 2024Article
- 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
- Passing the βAR: PI3Kγ Is the Judge of β Adrenergic Receptor Resensitization.Circulation research · 2023Article
- Hypoxia Sensing of β-Adrenergic Receptor Is Regulated by Endosomal PI3Kγ.Circulation research · 2023Article
- Stromal Vascular Fraction Restores Vasodilatory Function by Reducing Oxidative Stress in Aging-Induced Coronary Microvascular Disease.Antioxidants & redox signaling · 2023Article
- Thirty years of SET/TAF1β/I2PP2A: from the identification of the biological functions to its implications in cancer and Alzheimer's disease.Bioscience reports · 2022Review
- Sex differences in α-adrenergic receptor function contribute to impaired hypothalamic metaplasticity following chronic intermittent ethanol exposure.Alcoholism, clinical and experimental research · 2022Article
- Cardiac expression of microRNA-7 is associated with adverse cardiac remodeling.Scientific reports · 2021Article
- Aging-Induced Impairment of Vascular Function: Mitochondrial Redox Contributions and Physiological/Clinical Implications.Antioxidants & redox signaling · 2021Review
- Respiratory syncytial virus induces βScience signaling · 2021Article
- Activated Protein Phosphatase 2A Disrupts Nutrient Sensing Balance Between Mechanistic Target of Rapamycin Complex 1 and Adenosine Monophosphate-Activated Protein Kinase, Causing Sarcopenia in Alcohol-Associated Liver Disease.Hepatology (Baltimore, Md.) · 2021Article
- The IgG3 subclass of β1-adrenergic receptor autoantibodies is an endogenous biaser of β1AR signaling.Molecular biology of the cell · 2021Article
- Cofilin: A Promising Protein Implicated in Cancer Metastasis and Apoptosis.Frontiers in cell and developmental biology · 2021Review
- PP2A-B55 Holoenzyme Regulation and Cancer.Biomolecules · 2020Review
- Potential roles of PP2A-Rac1 signaling axis in pancreatic β-cell dysfunction under metabolic stress: Progress and promise.Biochemical pharmacology · 2020Review
- RTK signaling requires C3ar1/C5ar1 and IL-6R joint signaling to repress dominant PTEN, SOCS1/3 and PHLPP restraint.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Function, Regulation and Biological Roles of PI3Kγ Variants.Biomolecules · 2019Review
- The NMR-based characterization of the FTY720-SET complex reveals an alternative mechanism for the attenuation of the inhibitory SET-PP2A interaction.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- GnRH regulates the expression of its receptor accessory protein SET in pituitary gonadotropes.PloS one · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Phosphoinositide 3-kinase γ (PI3Kγ) is activated by G protein-coupled receptors (GPCRs). We show here that PI3Kγ inhibits protein phosphatase 2A (PP2A) at the β-adrenergic receptor (βAR, a GPCR) complex altering G protein coupling. PI3Kγ inhibition results in significant increase of βAR-associated phosphatase activity leading to receptor dephosphorylation and resensitization preserving cardiac function. Mechanistically, PI3Kγ inhibits PP2A activity at the βAR complex by phosphorylating an intracellular inhibitor of PP2A (I2PP2A) on serine residues 9 and 93, resulting in enhanced binding to PP2A. Indeed, enhanced phosphorylation of β2ARs is observed with a phosphomimetic I2PP2A mutant that was completely reversed with a mutant mimicking dephosphorylated state. siRNA depletion of endogenous I2PP2A augments PP2A activity despite active PI3K resulting in β2AR dephosphorylation and sustained signaling. Our study provides the underpinnings of a PI3Kγ-mediated regulation of PP2A activity that has significant consequences on receptor function with broad implications in cellular signaling.
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Registered trials
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.