Annexin A2 is SUMOylated on its N-terminal domain: regulation by insulin

FEBS Lett. 2015 Apr 13;589(9):985-91. doi: 10.1016/j.febslet.2015.03.007. Epub 2015 Mar 14.

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.

Keywords: Annexin A2; Endocytosis; Insulin; Insulin receptor; SUMOylation; Tyrosine phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Annexin A2 / chemistry
  • Annexin A2 / genetics*
  • Annexin A2 / metabolism
  • Binding Sites / genetics
  • Cell Line, Tumor
  • Endosomes / metabolism
  • Golgi Apparatus / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Immunoblotting
  • Insulin / pharmacology
  • Microtubules / metabolism
  • Mutation*
  • Protein Binding
  • Protein Interaction Maps
  • Receptor, Insulin / metabolism
  • SUMO-1 Protein / genetics
  • SUMO-1 Protein / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics*
  • Sumoylation / drug effects
  • Sumoylation / genetics*

Substances

  • Actins
  • Annexin A2
  • Hypoglycemic Agents
  • Insulin
  • SUMO-1 Protein
  • Receptor, Insulin