INVESTIGADORES
COLUCCIO LESKOW Federico
artículos
Título:
Insulin receptor membrane retention by a traceable chimeric mutant
Autor/es:
JIMENA GIUDICE; ELIZABETH A JARES-ERIJMAN; FEDERICO COLUCCIO LESKOW
Revista:
CELL COMMUNICATION AND SIGNALING
Editorial:
BIOMED CENTRAL LTD
Referencias:
Lugar: Londres; Año: 2013 vol. 11 p. 1 - 13
ISSN:
1478-811X
Resumen:
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.
Keywords: Insulin receptor, Membrane retention, Dominant negative, Endocytosis