title: Annexin A2 is SUMOylated on its N-terminal domain: regulation by insulin.
abstract: Insulin receptor (IR) endocytosis requires a remodelling of the actin cytoskeleton. We show here that ANXA2 is SUMOylated at the K10 located in a non-consensus SUMOylation motif in the N-terminal domain. The Y24F mutation decreased the SUMOylation signal, whereas insulin stimulation increased ANXA2 SUMOylation. A survey of protein SUMOylation in hepatic Golgi/endosome (G/E) fractions after insulin injections revealed the presence of a SUMOylation pattern and confirmed the SUMOylation of ANXA2. The construction of an IR/ANXA2/SUMO network (IRASGEN) in the G/E context reveals the presence of interacting nodes whereby SUMO1 connects ANXA2 to actin and microtubule-mediated changes in membrane topology. Heritable variants associated with type 2 diabetes represent 41% of the IRASGEN thus pointing out the physio-pathological importance of this subnetwork.
authors.affiliation: Département de Pédiatrie, Laboratoire de biologie cellulaire Centre de recherche du CHU de Québec, Université Laval, Québec, PQ, Canada.
authors.forename: Danielle
authors.initials: D
authors.lastname: Caron
authors.affiliation: Département de Pédiatrie, Laboratoire de biologie cellulaire Centre de recherche du CHU de Québec, Université Laval, Québec, PQ, Canada.
authors.forename: Martial
authors.initials: M
authors.lastname: Boutchueng-Djidjou
authors.affiliation: Institut de Biologie Intégrative et des Système (IBIS), Université Laval, Québec, PQ, Canada; Laboratory of Cellular and Developmental Genetics, Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec, PQ, Canada; PROTEO, Université Laval, Québec, PQ, Canada.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Tanguay
authors.affiliation: Département de Pédiatrie, Laboratoire de biologie cellulaire Centre de recherche du CHU de Québec, Université Laval, Québec, PQ, Canada. Electronic address: robert.faure@crchudequebec.ulaval.ca.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Faure
mesh_terms: D000199:Actins / Q000378:metabolism; D017306:Annexin A2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D011992:Endosomes / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D015151:Immunoblotting; D007328:Insulin / Q000494:pharmacology; D008870:Microtubules / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D060066:Protein Interaction Maps; D011972:Receptor, Insulin / Q000378:metabolism; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D058207:Sumoylation / Q000187:drug effects / Q000235:genetics*
chemical_list: D000199:Actins; D017306:Annexin A2; D007004:Hypoglycemic Agents; D007328:Insulin; D025842:SUMO-1 Protein; D011972:Receptor, Insulin
keywords: Annexin A2; Endocytosis; Insulin; Insulin receptor; SUMOylation; Tyrosine phosphorylation