An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytes

The MAL protein is an essential component of the specialized machinery for apical targeting in epithelial cells. The src family kinase Lck plays a pivotal role in T cell signaling. We show that MAL is required in T cells for efficient expression of Lck at the plasma membrane and activation of IL-2 t...

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Autores: Antón Hurtado, Olga María, Batista, Alicia, Millán, Jaime, Andrés-Delgado, Laura, Puertollano, Rosa, Correas, Isabel, Alonso, Miguel A.
Tipo de recurso: artículo
Fecha de publicación:2008
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/96980
Acceso en línea:https://hdl.handle.net/20.500.14352/96980
Access Level:acceso abierto
Palabra clave:Biología celular (Biología)
2412.07 Inmunoquímica
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spelling An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytesAntón Hurtado, Olga MaríaBatista, AliciaMillán, JaimeAndrés-Delgado, LauraPuertollano, RosaCorreas, IsabelAlonso, Miguel A.Biología celular (Biología)2412.07 InmunoquímicaThe MAL protein is an essential component of the specialized machinery for apical targeting in epithelial cells. The src family kinase Lck plays a pivotal role in T cell signaling. We show that MAL is required in T cells for efficient expression of Lck at the plasma membrane and activation of IL-2 transcription. To investigate the mechanism by which MAL regulates Lck targeting, we analyzed the dynamics of Lck and found that it travels to the plasma membrane in specific transport carriers containing MAL. Coimmunoprecipitation experiments indicated an association of MAL with Lck. Both carrier formation and partitioning of Lck into detergent-insoluble membranes were ablated in the absence of MAL. Polarization of T cell receptor for antigen (TCR) and microtubule-organizing center to immunological synapse (IS) were also defective. Although partial correction of the latter defects was possible by forced expression of Lck at the plasma membrane, their complete correction, formation of transport vesicles, partitioning of Lck, and restoration of signaling pathways, which are required for IL-2 transcription up-regulation, were achieved by exogenous expression of MAL. We concluded that MAL is required for recruitment of Lck to specialized membranes and formation of specific transport carriers for Lck targeting. This novel transport pathway is crucial for TCR-mediated signaling and IS assembly.Rockefeller University PressUniversidad Complutense de Madrid20082008-01-0120082008-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/96980reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/969802026-06-02T12:44:21Z
dc.title.none.fl_str_mv An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytes
title An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytes
spellingShingle An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytes
Antón Hurtado, Olga María
Biología celular (Biología)
2412.07 Inmunoquímica
title_short An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytes
title_full An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytes
title_fullStr An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytes
title_full_unstemmed An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytes
title_sort An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytes
dc.creator.none.fl_str_mv Antón Hurtado, Olga María
Batista, Alicia
Millán, Jaime
Andrés-Delgado, Laura
Puertollano, Rosa
Correas, Isabel
Alonso, Miguel A.
author Antón Hurtado, Olga María
author_facet Antón Hurtado, Olga María
Batista, Alicia
Millán, Jaime
Andrés-Delgado, Laura
Puertollano, Rosa
Correas, Isabel
Alonso, Miguel A.
author_role author
author2 Batista, Alicia
Millán, Jaime
Andrés-Delgado, Laura
Puertollano, Rosa
Correas, Isabel
Alonso, Miguel A.
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv Biología celular (Biología)
2412.07 Inmunoquímica
topic Biología celular (Biología)
2412.07 Inmunoquímica
description The MAL protein is an essential component of the specialized machinery for apical targeting in epithelial cells. The src family kinase Lck plays a pivotal role in T cell signaling. We show that MAL is required in T cells for efficient expression of Lck at the plasma membrane and activation of IL-2 transcription. To investigate the mechanism by which MAL regulates Lck targeting, we analyzed the dynamics of Lck and found that it travels to the plasma membrane in specific transport carriers containing MAL. Coimmunoprecipitation experiments indicated an association of MAL with Lck. Both carrier formation and partitioning of Lck into detergent-insoluble membranes were ablated in the absence of MAL. Polarization of T cell receptor for antigen (TCR) and microtubule-organizing center to immunological synapse (IS) were also defective. Although partial correction of the latter defects was possible by forced expression of Lck at the plasma membrane, their complete correction, formation of transport vesicles, partitioning of Lck, and restoration of signaling pathways, which are required for IL-2 transcription up-regulation, were achieved by exogenous expression of MAL. We concluded that MAL is required for recruitment of Lck to specialized membranes and formation of specific transport carriers for Lck targeting. This novel transport pathway is crucial for TCR-mediated signaling and IS assembly.
publishDate 2008
dc.date.none.fl_str_mv 2008
2008-01-01
2008
2008-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/96980
url https://hdl.handle.net/20.500.14352/96980
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 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 reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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