A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes

Ras proteins are small guanosine triphosphatases involved in the regulation of important cellular functions such as proliferation, differentiation, and apoptosis. Understanding the intracellular trafficking of Ras proteins is crucial to identify novel Ras signaling platforms. In this study, we repor...

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Detalles Bibliográficos
Autores: Lu, Albert, Tebar Ramon, Francesc, Alvarez-Moya, Blanca, López Alcalá, Cristina, Calvo Ademuz, Maria, Enrich Bastús, Carles, Agell i Jané, Neus, Nakamura, Takeshi, Matsuda, Michiyuki, Bachs Valldeneu, Oriol
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2009
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/25212
Acceso en línea:https://hdl.handle.net/2445/25212
Access Level:acceso abierto
Palabra clave:Proteïnes ras
Transducció de senyal cel·lular
Ras proteins
Cellular signal transduction
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spelling A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomesLu, AlbertTebar Ramon, FrancescAlvarez-Moya, BlancaLópez Alcalá, CristinaCalvo Ademuz, MariaEnrich Bastús, CarlesAgell i Jané, NeusNakamura, TakeshiMatsuda, MichiyukiBachs Valldeneu, OriolProteïnes rasTransducció de senyal cel·lularRas proteinsCellular signal transductionRas proteins are small guanosine triphosphatases involved in the regulation of important cellular functions such as proliferation, differentiation, and apoptosis. Understanding the intracellular trafficking of Ras proteins is crucial to identify novel Ras signaling platforms. In this study, we report that epidermal growth factor triggers Kirsten Ras (KRas) translocation onto endosomal membranes (independently of calmodulin and protein kinase C phosphorylation) through a clathrin-dependent pathway. From early endosomes, KRas but not Harvey Ras or neuroblastoma Ras is sorted and transported to late endosomes (LEs) and lysosomes. Using yellow fluorescent protein¿Raf1 and the Raichu-KRas probe, we identified for the first time in vivo¿active KRas on Rab7 LEs, eliciting a signal output through Raf1. On these LEs, we also identified the p14¿MP1 scaffolding complex and activated extracellular signal-regulated kinase 1/2. Abrogation of lysosomal function leads to a sustained late endosomal mitogen-activated protein kinase signal output. Altogether, this study reveals novel aspects about KRas intracellular trafficking and signaling, shedding new light on the mechanisms controlling Ras regulation in the cell.Rockefeller University Press201220122009info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion17 p.application/pdfhttps://hdl.handle.net/2445/25212Articles publicats en revistes (Biomedicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció digital del document publicat a: http://dx.doi.org/10.1083/jcb.200807186Journal of Cell Biology, 2009, vol. 184, núm. 6, p. 863-879http://dx.doi.org/10.1083/jcb.200807186(c) Rockefeller University Press, 2009info:eu-repo/semantics/openAccessoai:recercat.cat:2445/252122026-05-29T05:05:01Z
dc.title.none.fl_str_mv A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes
title A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes
spellingShingle A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes
Lu, Albert
Proteïnes ras
Transducció de senyal cel·lular
Ras proteins
Cellular signal transduction
title_short A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes
title_full A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes
title_fullStr A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes
title_full_unstemmed A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes
title_sort A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes
dc.creator.none.fl_str_mv Lu, Albert
Tebar Ramon, Francesc
Alvarez-Moya, Blanca
López Alcalá, Cristina
Calvo Ademuz, Maria
Enrich Bastús, Carles
Agell i Jané, Neus
Nakamura, Takeshi
Matsuda, Michiyuki
Bachs Valldeneu, Oriol
author Lu, Albert
author_facet Lu, Albert
Tebar Ramon, Francesc
Alvarez-Moya, Blanca
López Alcalá, Cristina
Calvo Ademuz, Maria
Enrich Bastús, Carles
Agell i Jané, Neus
Nakamura, Takeshi
Matsuda, Michiyuki
Bachs Valldeneu, Oriol
author_role author
author2 Tebar Ramon, Francesc
Alvarez-Moya, Blanca
López Alcalá, Cristina
Calvo Ademuz, Maria
Enrich Bastús, Carles
Agell i Jané, Neus
Nakamura, Takeshi
Matsuda, Michiyuki
Bachs Valldeneu, Oriol
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Proteïnes ras
Transducció de senyal cel·lular
Ras proteins
Cellular signal transduction
topic Proteïnes ras
Transducció de senyal cel·lular
Ras proteins
Cellular signal transduction
description Ras proteins are small guanosine triphosphatases involved in the regulation of important cellular functions such as proliferation, differentiation, and apoptosis. Understanding the intracellular trafficking of Ras proteins is crucial to identify novel Ras signaling platforms. In this study, we report that epidermal growth factor triggers Kirsten Ras (KRas) translocation onto endosomal membranes (independently of calmodulin and protein kinase C phosphorylation) through a clathrin-dependent pathway. From early endosomes, KRas but not Harvey Ras or neuroblastoma Ras is sorted and transported to late endosomes (LEs) and lysosomes. Using yellow fluorescent protein¿Raf1 and the Raichu-KRas probe, we identified for the first time in vivo¿active KRas on Rab7 LEs, eliciting a signal output through Raf1. On these LEs, we also identified the p14¿MP1 scaffolding complex and activated extracellular signal-regulated kinase 1/2. Abrogation of lysosomal function leads to a sustained late endosomal mitogen-activated protein kinase signal output. Altogether, this study reveals novel aspects about KRas intracellular trafficking and signaling, shedding new light on the mechanisms controlling Ras regulation in the cell.
publishDate 2009
dc.date.none.fl_str_mv 2009
2012
2012
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/25212
url https://hdl.handle.net/2445/25212
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció digital del document publicat a: http://dx.doi.org/10.1083/jcb.200807186
Journal of Cell Biology, 2009, vol. 184, núm. 6, p. 863-879
http://dx.doi.org/10.1083/jcb.200807186
dc.rights.none.fl_str_mv (c) Rockefeller University Press, 2009
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Rockefeller University Press, 2009
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 17 p.
application/pdf
dc.publisher.none.fl_str_mv Rockefeller University Press
publisher.none.fl_str_mv Rockefeller University Press
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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