ArticleProceedings of the National Academy of Sciences of the United States of America2008
The p110beta isoform of phosphoinositide 3-kinase signals downstream of G protein-coupled receptors and is functionally redundant with p110gamma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 187 papers.
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Who cites it
187 citing papers in PubMed, 340 citations in OpenAlex.
- Subcellular Cartography of the Phosphoinositide Multiverse.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2026Review
- 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
- The role of the striatin family proteins in hippo signaling and cellular regulation.Cell & bioscience · 2025Article
- Inositol and PIP2/PIP3 Ratio: At the Crossroad of the Biodynamic Interface Between Cells and Their Microenvironment.Biomolecules · 2025Review
- Targeting PI3K Signaling to Overcome Tumor Immunosuppression: Synergistic Strategies to Enhance Cancer Vaccine Efficacy.Vaccines · 2025Review
- Mesenchymal Stem Cell Derived Exosomes Alleviates Hirschsprung-Associated Enterocolitis by Inhibiting AKT Phosphorylation in Macrophages Through miR-223.Stem cells international · 2025Article
- Molecular Basis of Oncogenic PI3K Proteins.Cancers · 2024Review
- Article
- Modulation of miR-146b by N6-methyladenosine modification remodels tumor-associated macrophages and enhances anti-PD-1 therapy in colorectal cancer.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Subunit-selective PI3-kinase control of action strategies in the medial prefrontal cortex.Neurobiology of learning and memory · 2023Article
- Targeting Class I-II-III PI3Ks in Cancer Therapy: Recent Advances in Tumor Biology and Preclinical Research.Cancers · 2023Review
- G protein-coupled bile acid receptor 1 reduced hepatic immune response and inhibited NFκB, PI3K/AKT, and PKC/P38 MAPK signaling pathway in hybrid grouper.Journal of animal science · 2023Article
- Natural products modulate cell apoptosis: a promising way for treating endometrial cancer.Frontiers in pharmacology · 2023Review
- Functional specialization of different PI3K isoforms for the control of neuronal architecture, synaptic plasticity, and cognition.Science advances · 2022Article
- The role of phosphoinositide 3-kinases in immune-inflammatory responses: potential therapeutic targets for abdominal aortic aneurysm.Cell cycle (Georgetown, Tex.) · 2022Review
- The Pro-Fibrotic Response to Lens Injury Is Signaled in a PI3K Isoform-Specific Manner.Biomolecules · 2022Article
- PI3Kδ activity controls plasticity and discriminates between EMT and stemness based on distinct TGFβ signaling.Communications biology · 2022Article
- Class I PI3K regulatory subunits control differentiation of dendritic cell subsets and regulate Flt3L mediated signal transduction.Scientific reports · 2022Article
- Class I PI3K Biology.Current topics in microbiology and immunology · 2022Article
- KRASSub-cellular biochemistry · 2022Review
127 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
The p110 isoforms of phosphoinositide 3-kinase (PI3K) are acutely regulated by extracellular stimuli. The class IA PI3K catalytic subunits (p110alpha, p110beta, and p110delta) occur in complex with a Src homology 2 (SH2) domain-containing p85 regulatory subunit, which has been shown to link p110alpha and p110delta to Tyr kinase signaling pathways. The p84/p101 regulatory subunits of the p110gamma class IB PI3K lack SH2 domains and instead couple p110gamma to G protein-coupled receptors (GPCRs). Here, we show, using small-molecule inhibitors with selectivity for p110beta and cells derived from a p110beta-deficient mouse line, that p110beta is not a major effector of Tyr kinase signaling but couples to GPCRs. In macrophages, both p110beta and p110gamma contributed to Akt activation induced by the GPCR agonist complement 5a, but not by the Tyr kinase ligand colony-stimulating factor-1. In fibroblasts, which express p110beta but not p110gamma, p110beta mediated Akt activation by the GPCR ligands stromal cell-derived factor, sphingosine-1-phosphate, and lysophosphatidic acid but not by the Tyr kinase ligands PDGF, insulin, and insulin-like growth factor 1. Introduction of p110gamma in these cells reduced the contribution of p110beta to GPCR signaling. Taken together, these data show that p110beta and p110gamma can couple redundantly to the same GPCR agonists. p110beta, which shows a much broader tissue distribution than the leukocyte-restricted p110gamma, could thus provide a conduit for GPCR-linked PI3K signaling in the many cell types where p110gamma expression is low or absent.
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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.