Insulin receptor membrane retention by a traceable chimeric mutant

Autores
Giudice, Jimena; Jares, Elizabeth Andrea; Coluccio Leskow, Federico
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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; Argentina
Fil: Jares, Elizabeth Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono; Argentina
Fil: 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; Argentina
Materia
Insulin
Insulin receptor
Endocytosis
Membrane retention
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/2541
Acceder
id CONICETDig_0fc0816a9b935086505ef293686fb3c7
oai_identifier_str oai:ri.conicet.gov.ar:11336/2541
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Insulin receptor membrane retention by a traceable chimeric mutantGiudice, JimenaJares, Elizabeth AndreaColuccio Leskow, FedericoInsulinInsulin receptorEndocytosisMembrane retentionhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Background: 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; ArgentinaBiomed Central2013-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/2541Giudice, Jimena; Jares, Elizabeth Andrea; Coluccio Leskow, Federico; Insulin receptor membrane retention by a traceable chimeric mutant; Biomed Central; Cell Communication and Signaling; 11; 45; 6-2013; 1-131478-811Xenginfo:eu-repo/semantics/altIdentifier/doi/doi:10.1186/1478-811X-11-45info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707766/info:eu-repo/semantics/altIdentifier/url/http://link.springer.com/article/10.1186%2F1478-811X-11-45info:eu-repo/semantics/altIdentifier/url/http://www.biosignaling.com/content/11/1/45info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:10:48Zoai:ri.conicet.gov.ar:11336/2541instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:10:49.189CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Insulin receptor membrane retention by a traceable chimeric mutant
title Insulin receptor membrane retention by a traceable chimeric mutant
spellingShingle Insulin receptor membrane retention by a traceable chimeric mutant
Giudice, Jimena
Insulin
Insulin receptor
Endocytosis
Membrane retention
title_short Insulin receptor membrane retention by a traceable chimeric mutant
title_full Insulin receptor membrane retention by a traceable chimeric mutant
title_fullStr Insulin receptor membrane retention by a traceable chimeric mutant
title_full_unstemmed Insulin receptor membrane retention by a traceable chimeric mutant
title_sort Insulin receptor membrane retention by a traceable chimeric mutant
dc.creator.none.fl_str_mv Giudice, Jimena
Jares, Elizabeth Andrea
Coluccio Leskow, Federico
author Giudice, Jimena
author_facet Giudice, Jimena
Jares, Elizabeth Andrea
Coluccio Leskow, Federico
author_role author
author2 Jares, Elizabeth Andrea
Coluccio Leskow, Federico
author2_role author
author
dc.subject.none.fl_str_mv Insulin
Insulin receptor
Endocytosis
Membrane retention
topic Insulin
Insulin receptor
Endocytosis
Membrane retention
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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; Argentina
Fil: Jares, Elizabeth Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono; Argentina
Fil: 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; Argentina
description 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.
publishDate 2013
dc.date.none.fl_str_mv 2013-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/2541
Giudice, Jimena; Jares, Elizabeth Andrea; Coluccio Leskow, Federico; Insulin receptor membrane retention by a traceable chimeric mutant; Biomed Central; Cell Communication and Signaling; 11; 45; 6-2013; 1-13
1478-811X
url http://hdl.handle.net/11336/2541
identifier_str_mv Giudice, Jimena; Jares, Elizabeth Andrea; Coluccio Leskow, Federico; Insulin receptor membrane retention by a traceable chimeric mutant; Biomed Central; Cell Communication and Signaling; 11; 45; 6-2013; 1-13
1478-811X
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/doi:10.1186/1478-811X-11-45
info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707766/
info:eu-repo/semantics/altIdentifier/url/http://link.springer.com/article/10.1186%2F1478-811X-11-45
info:eu-repo/semantics/altIdentifier/url/http://www.biosignaling.com/content/11/1/45
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Biomed Central
publisher.none.fl_str_mv Biomed Central
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846083256337825792
score 13.22299

Publicaciones similares