دورية أكاديمية
PKCβ phosphorylates PI3Kγ to activate it and release it from GPCR control.
| العنوان: | PKCβ phosphorylates PI3Kγ to activate it and release it from GPCR control. |
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| المؤلفون: | Walser, Romy, Burke, John, E., Gogvadze, Elena, Bohnacker, Thomas, Zhang, Xuxiao, Hess, Daniel, Küenzi, Peter, Leitges, Michael, Hirsch, Emilio, Williams, Roger, L., Laffargue, Muriel, Wymann, Matthias, P. |
| المساهمون: | Department of Biomedicine, Laboratory of Molecular Biology, Medical Research Council, Friedrich Miescher Institute for Biomedical Research, Biotechnology center of Oslo, Faculty of Medicine Oslo, University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet Copenhagen, Copenhagen University Hospital-Copenhagen University Hospital, Department of Genetics, Biology and Biochemistry, Università degli studi di Torino = University of Turin (UNITO), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by the Swiss National Science Foundation (310030_127574 & 31EM30-126143, www.snf.ch), the ESF EuroMEMBRANE programme grant FP-018 (www.esf.org), and the Medical Research Council (file reference number U105184308). JEB was supported by an EMBO long-term fellowship (ALTF268-2009, www.embo.org) and the British Heart Foundation (PG11/109/29247, www.bhf.org.uk). |
| المصدر: | ISSN: 1544-9173. |
| بيانات النشر: | HAL CCSD Public Library of Science |
| سنة النشر: | 2013 |
| المجموعة: | Université Toulouse III - Paul Sabatier: HAL-UPS |
| مصطلحات موضوعية: | MESH: Animals, MESH: Calcium, MESH: Mice, Inbred C57BL, MESH: Models, Biological, Molecular, MESH: Phosphorylation, MESH: Phosphoserine, MESH: Protein Binding, MESH: Protein Kinase C beta, MESH: Protein Structure, Tertiary, MESH: Receptors, G-Protein-Coupled, MESH: Signal Transduction, MESH: Catalytic Domain, MESH: Thapsigargin, MESH: Cell Degranulation, MESH: Class Ib Phosphatidylinositol 3-Kinase, MESH: Enzyme Activation, MESH: Enzyme Stability, MESH: Extracellular Space, MESH: Mast Cells, [SDV.BC]Life Sciences [q-bio]/Cellular Biology |
| الوصف: | International audience ; 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/23824069; inserm-01055308; https://inserm.hal.science/inserm-01055308Test; https://inserm.hal.science/inserm-01055308/documentTest; https://inserm.hal.science/inserm-01055308/file/journal.pbio.1001587.pdfTest; PUBMED: 23824069 |
| DOI: | 10.1371/journal.pbio.1001587 |
| الإتاحة: | https://doi.org/10.1371/journal.pbio.1001587Test https://inserm.hal.science/inserm-01055308Test https://inserm.hal.science/inserm-01055308/documentTest https://inserm.hal.science/inserm-01055308/file/journal.pbio.1001587.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.D6FEB0A9 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1371/journal.pbio.1001587 |
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