Glucagon-mediated internalization of serine-phosphorylated glucagon receptor and Gsalpha in rat liver
| Autor: | Clémence Merlen, Sylvie Fabrega, Cecilia G. Unson, Bernard Desbuquois, François Authier |
|---|---|
| Přispěvatelé: | Signalisation et physiopathologie des cellules épithéliales, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Rockefeller University [New York], Codogno, Patrice, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), The rockefeller university, The Rockefeller University |
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Male
Arrestins MESH : GTP-Binding Protein alpha Subunits Gs MESH: Rats Sprague-Dawley MESH : Adenylate Cyclase Biochemistry Rats Sprague-Dawley MESH : Receptors Glucagon Phosphoserine Structural Biology GTP-Binding Protein alpha Subunits Gs Receptors Glucagon MESH: Animals Internalization beta-Arrestins media_common [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism 0303 health sciences MESH: Phosphoserine Endosomal protease MESH : Glucagon MESH : Rats MESH: Glucagon 030302 biochemistry & molecular biology digestive oral and skin physiology [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism Endocytosis beta-Arrestin 1 Liver MESH: Endocytosis MESH: Arrestins Signal transduction Glucagon receptor family hormones hormone substitutes and hormone antagonists Adenylyl Cyclases medicine.medical_specialty endocrine system G-protein MESH: Rats G protein MESH : Endocytosis MESH : Male media_common.quotation_subject MESH : Arrestins Biophysics [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Glucagon 03 medical and health sciences MESH: Receptors Glucagon MESH : Phosphoserine Internal medicine MESH: Adenylate Cyclase Genetics medicine Animals Molecular Biology [SDV.BC] Life Sciences [q-bio]/Cellular Biology Glucagon-like peptide 1 receptor 030304 developmental biology [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology MESH : Liver Cell Biology MESH: GTP-Binding Protein alpha Subunits Gs MESH : Rats Sprague-Dawley MESH: Male Rats Endocrinology MESH : Animals Intracellular signalling Glucagon receptor MESH: Liver |
| Zdroj: | FEBS Letters FEBS Letters, Wiley, 2006, 580 (24), pp.5697-704. ⟨10.1016/j.febslet.2006.09.021⟩ FEBS Letters, 2006, 580 (24), pp.5697-704. ⟨10.1016/j.febslet.2006.09.021⟩ FEBS Letters, Wiley, 2006, 580 (24), pp.5697-704. 〈10.1016/j.febslet.2006.09.021〉 |
| ISSN: | 0014-5793 1873-3468 |
| DOI: | 10.1016/j.febslet.2006.09.021⟩ |
| Popis: | To assess glucagon receptor compartmentalization and signal transduction in liver parenchyma, we have studied the functional relationship between glucagon receptor endocytosis, phosphorylation and coupling to the adenylate cyclase system. Following administration of a saturating dose of glucagon to rats, a rapid internalization of glucagon receptor was observed coincident with its serine phosphorylation both at the plasma membrane and within endosomes. Co-incident with glucagon receptor endocytosis, a massive internalization of both the 45- and 47-kDa Gsalpha proteins was also observed. In contrast, no change in the subcellular distribution of adenylate cyclase or beta-arrestin 1 and 2 was observed. In response to des-His(1)-[Glu(9)]glucagon amide, a glucagon receptor antagonist, the extent and rate of glucagon receptor endocytosis and Gsalpha shift were markedly reduced compared with wild-type glucagon. However, while the glucagon analog exhibited a wild-type affinity for endosomal acidic glucagonase activity and was processed at low pH with similar kinetics and rates, its proteolysis at neutral pH was 3-fold lower. In response to tetraiodoglucagon, a glucagon receptor agonist of enhanced biological potency, glucagon receptor endocytosis and Gsalpha shift were of higher magnitude and of longer duration, and a marked and prolonged activation of adenylate cyclase both at the plasma membrane and in endosomes was observed. The subsequent post-endosomal fate of internalized Gsalpha was evaluated in a cell-free rat liver endosome-lysosome fusion system following glucagon injection. A sustained endo-lysosomal transfer of the two 45- and 47-kDa Gsalpha isoforms was observed. Therefore, these results reveal that within hepatic target cells and consequent to glucagon-mediated internalization of the serine-phosphorylated glucagon receptor and the Gsalpha protein, extended signal transduction may occur in vivo at the locus of the endo-lysosomal apparatus. |
| Databáze: | OpenAIRE |
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