ArticlePLoS biology2013
PKCβ phosphorylates PI3Kγ to activate it and release it from GPCR control.
Article in PLoS biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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
25 citing papers in PubMed, 79 citations in OpenAlex.
- PI3Kγ in Tumour Inflammation: Bridging Immune Response and Cancer Progression-A Mini-Review.Immunology · 2025Review
- Metformin and the PI3K/AKT signaling pathway: implications for cancer, cardiovascular, and central nervous system diseases.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Article
- Allosteric activation or inhibition of PI3Kγ mediated through conformational changes in the p110γ helical domain.bioRxiv : the preprint server for biology · 2023Article
- Molecular basis for differential activation of p101 and p84 complexes of PI3Kγ by Ras and GPCRs.Cell reports · 2023Article
- The role of PI3Kγ in the immune system: new insights and translational implications.Nature reviews. Immunology · 2022Review
- Review
- PI3K and AKT at the Interface of Signaling and Metabolism.Current topics in microbiology and immunology · 2022Article
- Structure of the phosphoinositide 3-kinase (PI3K) p110γ-p101 complex reveals molecular mechanism of GPCR activation.Science advances · 2021Article
- Article
- Gβγ is a direct regulator of endogenous p101/p110γ and p84/p110γ PI3Kγ complexes in mouse neutrophils.Science signaling · 2020Article
- PI3K inhibitors in thrombosis and cardiovascular disease.Clinical and translational medicine · 2020Review
- PI3KFrontiers in immunology · 2020Article
- Function, Regulation and Biological Roles of PI3Kγ Variants.Biomolecules · 2019Review
- A class of highly selective inhibitors bind to an active state of PI3Kγ.Nature chemical biology · 2019Article
- Dynamic structural biology at the protein membrane interface.The Journal of biological chemistry · 2019Review
- Targeting PI3Kδ and PI3Kγ signalling disrupts human AML survival and bone marrow stromal cell mediated protection.Oncotarget · 2016Article
- Regulation of PI3K by PKC and MARCKS: Single-Molecule Analysis of a Reconstituted Signaling Pathway.Biophysical journal · 2016Article
- Using hydrogen deuterium exchange mass spectrometry to engineer optimized constructs for crystallization of protein complexes: Case study of PI4KIIIβ with Rab11.Protein science : a publication of the Protein Society · 2016Article
- p84 forms a negative regulatory complex with p110γ to control PI3Kγ signalling during cell migration.Immunology and cell biology · 2015Article
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 7 institutions in 5 countries.
Funding
Abstract
All class I phosphoinositide 3-kinases (PI3Ks) associate tightly with regulatory subunits through interactions that have been thought to be constitutive. PI3Kγ is key to the regulation of immune cell responses activated by G protein-coupled receptors (GPCRs). Remarkably we find that PKCβ phosphorylates Ser582 in the helical domain of the PI3Kγ catalytic subunit p110γ in response to clustering of the high-affinity IgE receptor (FcεRI) and/or store-operated Ca²⁺- influx in mast cells. Phosphorylation of p110γ correlates with the release of the p84 PI3Kγ adapter subunit from the p84-p110γ complex. Ser582 phospho-mimicking mutants show increased p110γ activity and a reduced binding to the p84 adapter subunit. As functional p84-p110γ is key to GPCR-mediated p110γ signaling, this suggests that PKCβ-mediated p110γ phosphorylation disconnects PI3Kγ from its canonical inputs from trimeric G proteins, and enables p110γ to operate downstream of Ca²⁺ and PKCβ. Hydrogen deuterium exchange mass spectrometry shows that the p84 adaptor subunit interacts with the p110γ helical domain, and reveals an unexpected mechanism of PI3Kγ regulation. Our data show that the interaction of p110γ with its adapter subunit is vulnerable to phosphorylation, and outline a novel level of PI3K control.
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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.