title: [Involvement of the endosomal compartment in cellular insulin signaling].
abstract: The insulin receptor and insulin signaling proteins downstream the receptor reside in different subcellular compartments and undergo redistribution within the cell upon insulin activation. Endocytosis of the insulin-receptor complex, by mediating ligand degradation and receptor dephosphorylation, is generally viewed as a mechanism which attenuates or arrests insulin signal transduction. However, several observations suggest that insulin receptor endocytosis and/or recruitement of insulin signaling proteins to endosomes are also involved in a positive regulation of insulin signaling: (1) upon internalization, the insulin receptor remains transiently phosphorylated and activated; (2) in insulin-stimulated cells or tissues, signaling proteins of the PI3K/Akt and Ras/Raf/Mek/Erk pathways are recruited to endosomes or other intracellular compartments, in which they undergo phosphorylation and/or activation; and (3) depletion or overexpression of proteins involved in the regulation of membrane trafficking and endocytosis interfere with insulin signaling. These observations support a spatial and temporal regulation of insulin signal transduction and reinforce the concept that, as for other membrane signaling receptors, endocytosis and signaling are functionally linked.
authors.affiliation: Inserm U1016 et CNRS UMR 8104, Institut Cochin, et Université Paris Descartes, 24 rue du Faubourg Saint Jacques, 75014 Paris, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Desbuquois
authors.affiliation: Service Information Scientifique et Technique (IST) de l'Inserm, Délégation Régionale Inserm Paris V, 2 rue d'Alésia, 75014 Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Authier
mesh_terms: D000818:Animals; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin; D051058:Oncogene Protein v-akt