Differential endocytosis and signaling dynamics of insulin receptor variants IR-A and IR-B

Autores
Giudice, Jimena; Coluccio Leskow, Federico; Arndt Jovin, Donna J.; Jovin, Thomas M.; Jares, Elizabeth Andrea
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Insulin signaling comprises a complex cascade of events, playing a key role in the regulation of glucose metabolism and cellular growth. Impaired response to insulin is the hallmark of diabetes, whereas upregulated insulin activity occurs in many cancers. Two splice variants of the insulin receptor (IR) exist in mammals: IR-A, lacking exon 11, and full-length IR-B. Although considerable biochemical data exist on insulin binding and downstream signaling, little is known about the dynamics of the IR itself. We created functional IR transgenes fused with visible fluorescent proteins for use in combination with biotinamido-caproyl insulin and streptavidin quantum dots. Using confocal and structured illumination microscopy, we visualized the endocytosis of both isoforms in living and fixed cells and demonstrated a higher rate of endocytosis of IR-A than IR-B. These differences correlated with higher and sustained activation of IR-A in response to insulin and with distinctive ERK1/2 activation profiles and gene transcription regulation. In addition, cells expressing IR-B showed higher AKT phosphorylation after insulin stimulation than cells expressing IR-A. Taken together, these results suggest that IR signaling is dependent on localization; internalized IRs regulate mitogenic activity, whereas metabolic balance signaling occurs at the cell membrane.
Fil: Giudice, Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Coluccio Leskow, Federico. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Arndt Jovin, Donna J.. Max Planck Institute for Biophysical Chemistry; Alemania
Fil: Jovin, Thomas M.. Max Planck Institute for Biophysical Chemistry; Alemania. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina
Materia
INSULIN
INSULIN RECEPTOR ISOFORMS
PROGRAMMABLE ARRAY MICROSCOPE
QUANTUM DOTS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/66648
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/66648
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Differential endocytosis and signaling dynamics of insulin receptor variants IR-A and IR-BGiudice, JimenaColuccio Leskow, FedericoArndt Jovin, Donna J.Jovin, Thomas M.Jares, Elizabeth AndreaINSULININSULIN RECEPTOR ISOFORMSPROGRAMMABLE ARRAY MICROSCOPEQUANTUM DOTShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Insulin signaling comprises a complex cascade of events, playing a key role in the regulation of glucose metabolism and cellular growth. Impaired response to insulin is the hallmark of diabetes, whereas upregulated insulin activity occurs in many cancers. Two splice variants of the insulin receptor (IR) exist in mammals: IR-A, lacking exon 11, and full-length IR-B. Although considerable biochemical data exist on insulin binding and downstream signaling, little is known about the dynamics of the IR itself. We created functional IR transgenes fused with visible fluorescent proteins for use in combination with biotinamido-caproyl insulin and streptavidin quantum dots. Using confocal and structured illumination microscopy, we visualized the endocytosis of both isoforms in living and fixed cells and demonstrated a higher rate of endocytosis of IR-A than IR-B. These differences correlated with higher and sustained activation of IR-A in response to insulin and with distinctive ERK1/2 activation profiles and gene transcription regulation. In addition, cells expressing IR-B showed higher AKT phosphorylation after insulin stimulation than cells expressing IR-A. Taken together, these results suggest that IR signaling is dependent on localization; internalized IRs regulate mitogenic activity, whereas metabolic balance signaling occurs at the cell membrane.Fil: Giudice, Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Coluccio Leskow, Federico. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Arndt Jovin, Donna J.. Max Planck Institute for Biophysical Chemistry; AlemaniaFil: Jovin, Thomas M.. Max Planck Institute for Biophysical Chemistry; Alemania. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Jares, Elizabeth Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; ArgentinaCompany of Biologists2011-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/66648Giudice, Jimena; Coluccio Leskow, Federico; Arndt Jovin, Donna J.; Jovin, Thomas M.; Jares, Elizabeth Andrea; Differential endocytosis and signaling dynamics of insulin receptor variants IR-A and IR-B; Company of Biologists; Journal of Cell Science; 124; 5; 3-2011; 801-8110021-9533CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1242/jcs.076869info:eu-repo/semantics/altIdentifier/url/http://jcs.biologists.org/content/124/5/801info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:06:13Zoai:ri.conicet.gov.ar:11336/66648instacron: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:34982025-09-03 10:06:13.932CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Differential endocytosis and signaling dynamics of insulin receptor variants IR-A and IR-B
title Differential endocytosis and signaling dynamics of insulin receptor variants IR-A and IR-B
spellingShingle Differential endocytosis and signaling dynamics of insulin receptor variants IR-A and IR-B
Giudice, Jimena
INSULIN
INSULIN RECEPTOR ISOFORMS
PROGRAMMABLE ARRAY MICROSCOPE
QUANTUM DOTS
title_short Differential endocytosis and signaling dynamics of insulin receptor variants IR-A and IR-B
title_full Differential endocytosis and signaling dynamics of insulin receptor variants IR-A and IR-B
title_fullStr Differential endocytosis and signaling dynamics of insulin receptor variants IR-A and IR-B
title_full_unstemmed Differential endocytosis and signaling dynamics of insulin receptor variants IR-A and IR-B
title_sort Differential endocytosis and signaling dynamics of insulin receptor variants IR-A and IR-B
dc.creator.none.fl_str_mv Giudice, Jimena
Coluccio Leskow, Federico
Arndt Jovin, Donna J.
Jovin, Thomas M.
Jares, Elizabeth Andrea
author Giudice, Jimena
author_facet Giudice, Jimena
Coluccio Leskow, Federico
Arndt Jovin, Donna J.
Jovin, Thomas M.
Jares, Elizabeth Andrea
author_role author
author2 Coluccio Leskow, Federico
Arndt Jovin, Donna J.
Jovin, Thomas M.
Jares, Elizabeth Andrea
author2_role author
author
author
author
dc.subject.none.fl_str_mv INSULIN
INSULIN RECEPTOR ISOFORMS
PROGRAMMABLE ARRAY MICROSCOPE
QUANTUM DOTS
topic INSULIN
INSULIN RECEPTOR ISOFORMS
PROGRAMMABLE ARRAY MICROSCOPE
QUANTUM DOTS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Insulin signaling comprises a complex cascade of events, playing a key role in the regulation of glucose metabolism and cellular growth. Impaired response to insulin is the hallmark of diabetes, whereas upregulated insulin activity occurs in many cancers. Two splice variants of the insulin receptor (IR) exist in mammals: IR-A, lacking exon 11, and full-length IR-B. Although considerable biochemical data exist on insulin binding and downstream signaling, little is known about the dynamics of the IR itself. We created functional IR transgenes fused with visible fluorescent proteins for use in combination with biotinamido-caproyl insulin and streptavidin quantum dots. Using confocal and structured illumination microscopy, we visualized the endocytosis of both isoforms in living and fixed cells and demonstrated a higher rate of endocytosis of IR-A than IR-B. These differences correlated with higher and sustained activation of IR-A in response to insulin and with distinctive ERK1/2 activation profiles and gene transcription regulation. In addition, cells expressing IR-B showed higher AKT phosphorylation after insulin stimulation than cells expressing IR-A. Taken together, these results suggest that IR signaling is dependent on localization; internalized IRs regulate mitogenic activity, whereas metabolic balance signaling occurs at the cell membrane.
Fil: Giudice, Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Coluccio Leskow, Federico. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Arndt Jovin, Donna J.. Max Planck Institute for Biophysical Chemistry; Alemania
Fil: Jovin, Thomas M.. Max Planck Institute for Biophysical Chemistry; Alemania. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina
description Insulin signaling comprises a complex cascade of events, playing a key role in the regulation of glucose metabolism and cellular growth. Impaired response to insulin is the hallmark of diabetes, whereas upregulated insulin activity occurs in many cancers. Two splice variants of the insulin receptor (IR) exist in mammals: IR-A, lacking exon 11, and full-length IR-B. Although considerable biochemical data exist on insulin binding and downstream signaling, little is known about the dynamics of the IR itself. We created functional IR transgenes fused with visible fluorescent proteins for use in combination with biotinamido-caproyl insulin and streptavidin quantum dots. Using confocal and structured illumination microscopy, we visualized the endocytosis of both isoforms in living and fixed cells and demonstrated a higher rate of endocytosis of IR-A than IR-B. These differences correlated with higher and sustained activation of IR-A in response to insulin and with distinctive ERK1/2 activation profiles and gene transcription regulation. In addition, cells expressing IR-B showed higher AKT phosphorylation after insulin stimulation than cells expressing IR-A. Taken together, these results suggest that IR signaling is dependent on localization; internalized IRs regulate mitogenic activity, whereas metabolic balance signaling occurs at the cell membrane.
publishDate 2011
dc.date.none.fl_str_mv 2011-03
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/11336/66648
Giudice, Jimena; Coluccio Leskow, Federico; Arndt Jovin, Donna J.; Jovin, Thomas M.; Jares, Elizabeth Andrea; Differential endocytosis and signaling dynamics of insulin receptor variants IR-A and IR-B; Company of Biologists; Journal of Cell Science; 124; 5; 3-2011; 801-811
0021-9533
CONICET Digital
CONICET
url http://hdl.handle.net/11336/66648
identifier_str_mv Giudice, Jimena; Coluccio Leskow, Federico; Arndt Jovin, Donna J.; Jovin, Thomas M.; Jares, Elizabeth Andrea; Differential endocytosis and signaling dynamics of insulin receptor variants IR-A and IR-B; Company of Biologists; Journal of Cell Science; 124; 5; 3-2011; 801-811
0021-9533
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1242/jcs.076869
info:eu-repo/semantics/altIdentifier/url/http://jcs.biologists.org/content/124/5/801
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Company of Biologists
publisher.none.fl_str_mv Company of Biologists
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
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score 13.13397

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