Academic Journal
PI3K-C2γ is a Rab5 effector selectively controlling endosomal Akt2 activation downstream of insulin signalling
| العنوان: | PI3K-C2γ is a Rab5 effector selectively controlling endosomal Akt2 activation downstream of insulin signalling |
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| المؤلفون: | L. Braccini, E. Ciraolo, C. C. Campa, A. Perino, D. L. Longo, G. Tibolla, M. Pregnolato, Y. Cao, B. Tassone, F. Damilano, M. Laffargue, E. Calautti, M. Falasca, G.D. Norata, J. M. Backer, E. Hirsch |
| المساهمون: | L. Braccini, E. Ciraolo, C.C. Campa, A. Perino, D.L. Longo, G. Tibolla, M. Pregnolato, Y. Cao, B. Tassone, F. Damilano, M. Laffargue, E. Calautti, M. Falasca, G.D. Norata, J.M. Backer, E. Hirsch |
| سنة النشر: | 2015 |
| المجموعة: | The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| مصطلحات موضوعية: | Settore BIO/14 - Farmacologia, Settore MED/13 - Endocrinologia |
| الوصف: | In the liver, insulin-mediated activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is at the core of metabolic control. Multiple PI3K and Akt isoenzymes are found in hepatocytes and whether isoform-selective interplays exist is currently unclear. Here we report that insulin signalling triggers the association of the liver-specific class II PI3K isoform γ (PI3K-C2γ) with Rab5-GTP, and its recruitment to Rab5-positive early endosomes. In these vesicles, PI3K-C2γ produces a phosphatidylinositol-3,4-bisphosphate pool specifically required for delayed and sustained endosomal Akt2 stimulation. Accordingly, loss of PI3K-C2γ does not affect insulin-dependent Akt1 activation as well as S6K and FoxO1-3 phosphorylation, but selectively reduces Akt2 activation, which specifically inhibits glycogen synthase activity. As a consequence, PI3K-C2γ-deficient mice display severely reduced liver accumulation of glycogen and develop hyperlipidemia, adiposity as well as insulin resistance with age or after consumption of a high-fat diet. Our data indicate PI3K-C2γ supports an isoenzyme-specific forking of insulin-mediated signal transduction to an endosomal pool of Akt2, required for glucose homeostasis. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/26100075; info:eu-repo/semantics/altIdentifier/wos/WOS:000357175700002; volume:6; firstpage:1; lastpage:15; numberofpages:15; journal:NATURE COMMUNICATIONS; http://hdl.handle.net/2434/286680; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84930184555 |
| DOI: | 10.1038/ncomms8400 |
| الاتاحة: | http://hdl.handle.net/2434/286680 https://doi.org/10.1038/ncomms8400 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.8135E6D0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/ncomms8400 |
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