Insulin receptor membrane retention by a traceable chimeric mutant

Cell Communication and Signaling

Research

Federico Coluccio Leskow¹  Jimena Giudice²  Elizabeth A Jares-Erijman³ 

[1] Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales (FCEN), Universidad de Buenos Aires (UBA) IQUIBICEN, CONICET, Intendente Güiraldes 2160, Ciudad Universitaria, C1428EGA, Argentina;Departamento de Ciencias Básicas, Universidad Nacional de Luján, Buenos Aires, Argentina;Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales (FCEN), Universidad de Buenos Aires (UBA) IQUIBICEN, CONICET, Intendente Güiraldes 2160, Ciudad Universitaria, C1428EGA, Argentina;Departamento de Química Orgánica, FCEN UBA CIHIDECAR, CONICET, C1428EGA, Buenos Aires, Argentina;Department of Pathology and Immunology, Baylor College of Medicine, One Baylor Plaza, 77030, Houston, TX, USA;Departamento de Química Orgánica, FCEN UBA CIHIDECAR, CONICET, C1428EGA, Buenos Aires, Argentina;

关键词: Insulin receptor;    Membrane retention;    Dominant negative;    Endocytosis;   

DOI  :  10.1186/1478-811X-11-45

 received in 2013-04-22, accepted in 2013-06-17,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsWe 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.ConclusionsThese results suggest that the mutant acts as a selective dominant negative blocking IR internalization-mediated signaling.

【 授权许可】

Unknown   
© Giudice et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.