Insulin receptor membrane retention by a traceable chimeric mutant

Background: The insulin receptor (IR) regulates glucose homeostasis, cell growth and differentiation. It has been hypothesized that the specific signaling characteristics of IR are in part determined by ligand-receptor complexes localization. Downstream signaling could be triggered from the plasma membrane or from endosomes. Regulation of activated receptor's internalization has been proposed as the mechanism responsible for the differential isoform and ligand-specific signaling. Results: We generated a traceable IR chimera that allows the labeling of the receptor at the cell surface. This mutant binds insulin but fails to get activated and internalized. However, the mutant heterodimerizes with wild type IR inhibiting its auto-phosphorylation and blocking its internalization. IR membrane retention attenuates AP-1 transcriptional activation favoring Akt activation. Conclusions: These results suggest that the mutant acts as a selective dominant negative blocking IR internalization-mediated signaling.Fil: Giudice, Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica; ArgentinaFil: Jares, Elizabeth Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono; ArgentinaFil: Coluccio Leskow, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica; Argentina. Universidad Nacional de Luján. Departamento de Ciencias Básicas; Argentin