ArticleScience signaling2016
Coincident signals from GPCRs and receptor tyrosine kinases are uniquely transduced by PI3Kβ in myeloid cells.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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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
36 citing papers in PubMed, 68 citations in OpenAlex.
- Article
- Novel role for PI3Kβ in placental function through regulation of system A amino acid transporter expression, associated with embryonic lethality.Cellular and molecular life sciences : CMLS · 2025Article
- Senescent B cells regulate CD38 expression via FOXO1 in pneumonia resulting fromLife medicine · 2025Article
- CDS2 expression regulates de novo phosphatidic acid synthesis.The Biochemical journal · 2024Article
- A class I PI3K signalling network regulates primary cilia disassembly in normal physiology and disease.Nature communications · 2024Article
- Targeting a lineage-specific PI3Kɣ-Akt signaling module in acute myeloid leukemia using a heterobifunctional degrader molecule.Nature cancer · 2024Article
- Article
- Signaling pathways that activate hepatic stellate cells during liver fibrosis.Frontiers in medicine · 2024Review
- Acyl chain selection couples the consumption and synthesis of phosphoinositides.The EMBO journal · 2022Article
- Calcium sensing receptor stimulates breast cancer cell migration via the Gβγ-AKT-mTORC2 signaling pathway.Journal of cell communication and signaling · 2022Article
- PIPFEBS letters · 2022Article
- Regulation of Neutrophil NADPH Oxidase, NOX2: A Crucial Effector in Neutrophil Phenotype and Function.Frontiers in cell and developmental biology · 2022Review
- Targeting PI3K by Natural Products: A Potential Therapeutic Strategy for Attention-deficit Hyperactivity Disorder.Current neuropharmacology · 2022Review
- Crosstalk between circRNAs and the PI3K/AKT signaling pathway in cancer progression.Signal transduction and targeted therapy · 2021Review
- TRPM2 ion channels steer neutrophils towards a source of hydrogen peroxide.Scientific reports · 2021Article
- The immunomodulatory effects of endocrine therapy in breast cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- Monitoring Phosphoinositide Fluxes and Effectors During Leukocyte Chemotaxis and Phagocytosis.Frontiers in cell and developmental biology · 2021Review
- Topical Application of the PI3Kβ-Selective Small Molecule Inhibitor TGX-221 Is an Effective Treatment Option for Experimental Epidermolysis Bullosa Acquisita.Frontiers in medicine · 2021Article
- Gβγ is a direct regulator of endogenous p101/p110γ and p84/p110γ PI3Kγ complexes in mouse neutrophils.Science signaling · 2020Article
- C5a impairs phagosomal maturation in the neutrophil through phosphoproteomic remodeling.JCI insight · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Class I phosphoinositide 3-kinases (PI3Ks) catalyze production of the lipid messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3), which plays a central role in a complex signaling network regulating cell growth, survival, and movement. This network is overactivated in cancer and inflammation, and there is interest in determining the PI3K catalytic subunit (p110α, p110β, p110γ, or p110δ) that should be targeted in different therapeutic contexts. Previous studies have defined unique regulatory inputs for p110β, including direct interaction with Gβγ subunits, Rac, and Rab5. We generated mice with knock-in mutations of p110β that selectively blocked the interaction with Gβγ and investigated its contribution to the PI3K isoform dependency of receptor tyrosine kinase (RTK) and G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR) responses in primary macrophages and neutrophils. We discovered a unique role for p110β in supporting synergistic PIP3 formation in response to the coactivation of macrophages by macrophage colony-stimulating factor (M-CSF) and the complement protein C5a. In contrast, we found partially redundant roles for p110α, p110β, and p110δ downstream of M-CSF alone and a nonredundant role for p110γ downstream of C5a alone. This role for p110β completely depended on direct interaction with Gβγ, suggesting that p110β transduces GPCR signals in the context of coincident activation by an RTK. The p110β-Gβγ interaction was also required for neutrophils to generate reactive oxygen species in response to the Fcγ receptor-dependent recognition of immune complexes and for their β2 integrin-mediated adhesion to fibrinogen or poly-RGD+, directly implicating heterotrimeric G proteins in these two responses.
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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.