TAILIEUCHUNG - Báo cáo khoa học: Compartmentalization and in vivo insulin-induced translocation of the insulin-signaling inhibitor Grb14 in rat liver

The molecular adaptor Grb14 bindsin vitro to the activated insulin receptor (IR) and inhibits IR signaling. In this study, we have used rat liver subcel-lular fractionation to analyze in vivo insulin effects on Grb14 compartmen-talization and IR phosphorylation and activity. | ỊFEBS Journal Compartmentalization and in vivo insulin-induced translocation of the insulin-signaling inhibitor Grb14 in rat liver Bernard Desbuquois1 2 Veronique Bereziat3 Francois Authier4 Jean Girard1 2 and Anne-Franọoise Burnol1 2 1 Institut Cochin Université Paris Descartes CNRS UMR 8104 France 2 Inserm U567 Paris France 3 Centre de Recherche Saint-Antoine UMR S893 Faculte de Medecine Pierre et Marie Curie Paris France 4 Inserm U756 Faculte de Pharmacie Paris 11 Chatenay-Malabry France Keywords endocytosis insulin receptor liver molecular adaptor tyrosine kinase activity Correspondence B. Desbuquois Departement d Endocrinologie Metabolisme Cancer Institut Cochin 24 rue du Faubourg Saint-Jacques 75014 Paris France Fax 33 1 44 41 24 21 Tel 33 1 53 73 27 08 E-mail Received 14 September 2007 revised 29 April 2008 accepted 2 July 2008 doi The molecular adaptor Grb14 binds in vitro to the activated insulin receptor IR and inhibits IR signaling. In this study we have used rat liver subcel-lular fractionation to analyze in vivo insulin effects on Grb14 compartmentalization and IR phosphorylation and activity. In control rats Grb14 was recovered mainly in microsomal and cytosolic fractions but was also detectable at low levels in plasma membrane and Golgi endosome fractions. Insulin injection led to a rapid and dose-dependent increase in Grb14 content first in the plasma membrane fraction and then in the Golgi endosome fraction which paralleled the increase in IR p-subunit tyrosine phosphorylation. Upon sustained in vivo IR tyrosine phosphorylation induced by high-affinity insulin analogs in vitro IR dephosphorylation by endogenous phosphatases and in vivo phosphorylation of the IR induced by injection of bisperoxo 1 10 phenanthroline oxovanadate a phosphotyrosine phosphatase inhibitor we observed a striking correlation between IR phosphorylation state and Grb14 content in both the plasma membrane and Golgi

• Báo cáo khoa học
• Report medicine
• traditional medicine
• scientific reports
• immune system
• Antimicrobial
• biosynthesis
• medical knowledge
• medical research
• analysis of cytoplasmic
• oxidation
• Crystal structure
• bacteria
• hemoglobin
• medicine
• cell proliferation
• breast cancer
• chemical reaction
• gastric cancer
• hormone medicine
• tumor cells
• biochemical studies
• environmental medicine