ArticleProceedings of the National Academy of Sciences of the United States of America2013
Molecular determinants of PI3Kγ-mediated activation downstream of G-protein-coupled receptors (GPCRs).
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
75 citing papers in PubMed, 137 citations in OpenAlex.
- PI3Kδ is selectively inhibited by roginolisib by stabilizing the C-terminal helix kα12.Nature communications · 2026Article
- Reconstitution of Ras-PI3Kγ membrane communication and feedback using light-induced signaling inputs.Nature communications · 2026Article
- Use of hydrogen deuterium exchange mass spectrometry in tandem with modern structural biology.The Biochemical journal · 2026Review
- Selective phosphoinositide 3-kinase inhibitors and implication in diabetic retinopathy as pharmacological tools.Frontiers in pharmacology · 2026Review
- Logic-based machine learning predicts how escitalopram attenuates cardiomyocyte hypertrophy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- GABAMolecular cell · 2025Article
- Targeting myeloid cells to improve cancer immune therapy.Frontiers in immunology · 2025Review
- Aloe emodin promotes mucosal healing by modifying the differentiation fate of enteroendocrine cellsActa pharmaceutica Sinica. B · 2024Article
- Molecular basis for Gβγ-mediated activation of phosphoinositide 3-kinase γ.Nature structural & molecular biology · 2024Article
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- Allosteric activation or inhibition of PI3Kγ mediated through conformational changes in the p110γ helical domain.bioRxiv : the preprint server for biology · 2023Article
- Molecular Mechanisms of PTH/PTHrP Class B GPCR Signaling and Pharmacological Implications.Endocrine reviews · 2023Article
- Beyond PI3Ks: targeting phosphoinositide kinases in disease.Nature reviews. Drug discovery · 2023Review
- Molecular basis for differential activation of p101 and p84 complexes of PI3Kγ by Ras and GPCRs.Cell reports · 2023Article
- Nonsense-mediated mRNA decay promote C2C12 cell proliferation by targeting PIK3R5.Journal of muscle research and cell motility · 2023Article
- The spatial distribution of GPCR and Gβγ activity across a cell dictates PIP3 dynamics.Scientific reports · 2023Article
- Inhibition of signaling downstream of beta-2 adrenoceptor by propranolol in prostate cancer cells.The Prostate · 2023Article
- Silencing of IRF8 Mediated by m6A Modification Promotes the Progression of T-Cell Acute Lymphoblastic Leukemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Role of Phosphoinositide 3-Kinase in Regulation of NOX-Derived Reactive Oxygen Species in Cancer.Antioxidants (Basel, Switzerland) · 2022Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Phosphoinositide 3-kinase gamma (PI3Kγ) has profound roles downstream of G-protein-coupled receptors in inflammation, cardiac function, and tumor progression. To gain insight into how the enzyme's activity is shaped by association with its p101 adaptor subunit, lipid membranes, and Gβγ heterodimers, we mapped these regulatory interactions using hydrogen-deuterium exchange mass spectrometry. We identify residues in both the p110γ and p101 subunits that contribute critical interactions with Gβγ heterodimers, leading to PI3Kγ activation. Mutating Gβγ-interaction sites of either p110γ or p101 ablates G-protein-coupled receptor-mediated signaling to p110γ/p101 in cells and severely affects chemotaxis and cell transformation induced by PI3Kγ overexpression. Hydrogen-deuterium exchange mass spectrometry shows that association with the p101 regulatory subunit causes substantial protection of the RBD-C2 linker as well as the helical domain of p110γ. Lipid interaction massively exposes that same helical site, which is then stabilized by Gβγ. Membrane-elicited conformational change of the helical domain could help prepare the enzyme for Gβγ binding. Our studies and others identify the helical domain of the class I PI3Ks as a hub for diverse regulatory interactions that include the p101, p87 (also known as p84), and p85 adaptor subunits; Rab5 and Gβγ heterodimers; and the β-adrenergic receptor kinase.
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What OpenQuestion holds
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.