FGFR2-Cbl interaction in lipid rafts triggers attenuation of PI3K/Akt signaling and osteoblast survival
| العنوان: | FGFR2-Cbl interaction in lipid rafts triggers attenuation of PI3K/Akt signaling and osteoblast survival |
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| المؤلفون: | Archana Sanjay, Pierre J. Marie, Hind Guenou, Cécilie Dufour, Daniel Bouvard, Karim Kaabeche |
| المساهمون: | Os et articulations, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dynamique des systèmes d'adhérence et différenciation (DySAD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Marie, Pierre |
| المصدر: | BONE BONE, Elsevier, 2008, 42 (6), pp.1032-9. ⟨10.1016/j.bone.2008.02.009⟩ BONE, 2008, 42 (6), pp.1032-9. ⟨10.1016/j.bone.2008.02.009⟩ |
| بيانات النشر: | HAL CCSD, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | MESH: Signal Transduction, Physiology, Endocrinology, Diabetes and Metabolism, MESH: Membrane Microdomains, Apoptosis, chemistry.chemical_compound, Phosphatidylinositol 3-Kinases, Ubiquitin, MESH: Proto-Oncogene Proteins c-cbl, Proto-Oncogene Proteins c-cbl, Lipid raft, 0303 health sciences, 030302 biochemistry & molecular biology, Osteoblast, Cell biology, medicine.anatomical_structure, MESH: Cell Survival, Fibroblast growth factor receptor, embryonic structures, Signal Transduction, musculoskeletal diseases, congenital, hereditary, and neonatal diseases and abnormalities, Histology, MESH: Receptor, Fibroblast Growth Factor, Type 2, MESH: Ubiquitin, MESH: Mutation, Cell Survival, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Cell Line, 03 medical and health sciences, Membrane Microdomains, medicine, Humans, Phosphatidylinositol, Receptor, Fibroblast Growth Factor, Type 2, Protein kinase B, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, PI3K/AKT/mTOR pathway, 030304 developmental biology, MESH: Osteoblasts, Osteoblasts, MESH: Humans, MESH: Proto-Oncogene Proteins c-akt, MESH: Apoptosis, MESH: 1-Phosphatidylinositol 3-Kinase, MESH: Cell Line, stomatognathic diseases, chemistry, Mutation, biology.protein, Proto-Oncogene Proteins c-akt |
| الوصف: | International audience; Fibroblast growth factor receptor (FGFR) signaling plays an important role in skeletogenesis. The molecular mechanisms triggered by activated FGFR in bone forming cells are however not fully understood. In this study, we identify a role for phosphatidylinositol 3-kinase (PI3K) signaling in cell apoptosis induced by FGFR2 activation in osteoblasts. We show that FGFR2 activation leads to decrease PI3K protein levels, resulting in attenuation of PI3K signaling in human osteoblasts. Biochemical and molecular analyses revealed that the attenuated PI3K signaling induced by FGFR2 activation is due to increased Cbl-PI3K molecular interaction mediated by the Cbl Y731 residue, which results in increased PI3K ubiquitination and proteasome degradation. Biochemical and immunocytochemical analyses showed that FGFR2 and Cbl interact in raft micro-domains at the plasma membrane. FGFR2 activation increases FGFR2 and Cbl recruitment in micro-domains, resulting in increased molecular interactions. Consistently, functional analyses showed that the attenuation of PI3K/Akt signaling triggered by FGFR2 activation results in increased osteoblast apoptosis. These results identify a functional molecular mechanism by which activated FGFR2 recruits Cbl in raft micro-domains to trigger PI3K ubiquitination and proteasome degradation, and reveal a novel role for PI3K/Akt attenuation in the control of osteoblast survival by FGFR2 signaling. |
| اللغة: | English |
| تدمد: | 8756-3282 |
| DOI: | 10.1016/j.bone.2008.02.009⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::baebb583dad90f441a8ae9dfed7522fc https://www.hal.inserm.fr/inserm-00346884 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....baebb583dad90f441a8ae9dfed7522fc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 87563282 |
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| DOI: | 10.1016/j.bone.2008.02.009⟩ |