Up-regulated expression of MICA on activated T lymphocytes involves Lck and Fyn kinases, and signaling through MEK1/ERK, p38 MAP kinase and calcineurin

Autores
Molinero, Luciana Lorena; Fuertes, Mercedes Beatriz; Fainboim, Leonardo; Rabinovich, Gabriel Adrián; Zwirner, Norberto Walter
Año de publicación
2003
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Major histocompatibility complex class I-related chain (MICA) is a cell stress-regulated molecule recognized by cytotoxic cells expressing the NKG2D molecule. MICA can be induced on T cells after CD3 or CD28 engagement. Here, we investigated the intracellular pathways leading to activation-induced expression of MICA. The Src kinase inhibitor PP1 inhibited up-regulated expression of MICA on anti-CD3-stimulated T cells. Downstream signaling routes involved mitogen-activated protein kinase (MAPK) kinase (MEK)1/extracellular signal-regulated kinase (ERK), p38 MAPK, and calcineurin, as MICA expression was prevented by U0126, SB202190, cyclosporin A, and FK506. Also, Lck and Fyn as well as MEK1/ERK and p38 MAPK were found to regulate MICA expression in anti-CD28/phorbol 12-myristate 13-acetate-stimulated T cells. Expression of MICA on activated T cells involved interleukin-2-dependent signaling routes triggered by Janus tyrosine kinases/signal transducer and activators of transcription and p70S6 kinase, as it could be inhibited by AG490 and rapamycin. This is the first demonstration of the intracellular pathways involved in activation-induced expression of MICA, which may reveal potential targets for immune intervention to modulate MICA expression in pathological disorders.
Fil: Molinero, Luciana Lorena. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Fuertes, Mercedes Beatriz. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Fainboim, Leonardo. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Rabinovich, Gabriel Adrián. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Zwirner, Norberto Walter. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Materia
Major Histocompatibiblity Complex
Signaling Pathways
Nkg2d
Mica
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:11336/36414
Acceder
id CONICETDig_d21d5d38e924e6e105504ebc13c93e03
oai_identifier_str oai:ri.conicet.gov.ar:11336/36414
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Up-regulated expression of MICA on activated T lymphocytes involves Lck and Fyn kinases, and signaling through MEK1/ERK, p38 MAP kinase and calcineurinMolinero, Luciana LorenaFuertes, Mercedes BeatrizFainboim, LeonardoRabinovich, Gabriel AdriánZwirner, Norberto WalterMajor Histocompatibiblity ComplexSignaling PathwaysNkg2dMicahttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Major histocompatibility complex class I-related chain (MICA) is a cell stress-regulated molecule recognized by cytotoxic cells expressing the NKG2D molecule. MICA can be induced on T cells after CD3 or CD28 engagement. Here, we investigated the intracellular pathways leading to activation-induced expression of MICA. The Src kinase inhibitor PP1 inhibited up-regulated expression of MICA on anti-CD3-stimulated T cells. Downstream signaling routes involved mitogen-activated protein kinase (MAPK) kinase (MEK)1/extracellular signal-regulated kinase (ERK), p38 MAPK, and calcineurin, as MICA expression was prevented by U0126, SB202190, cyclosporin A, and FK506. Also, Lck and Fyn as well as MEK1/ERK and p38 MAPK were found to regulate MICA expression in anti-CD28/phorbol 12-myristate 13-acetate-stimulated T cells. Expression of MICA on activated T cells involved interleukin-2-dependent signaling routes triggered by Janus tyrosine kinases/signal transducer and activators of transcription and p70S6 kinase, as it could be inhibited by AG490 and rapamycin. This is the first demonstration of the intracellular pathways involved in activation-induced expression of MICA, which may reveal potential targets for immune intervention to modulate MICA expression in pathological disorders.Fil: Molinero, Luciana Lorena. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Fuertes, Mercedes Beatriz. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Fainboim, Leonardo. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Rabinovich, Gabriel Adrián. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Zwirner, Norberto Walter. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFederation of American Societies for Experimental Biology2003-06-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/36414Molinero, Luciana Lorena; Fuertes, Mercedes Beatriz; Fainboim, Leonardo; Rabinovich, Gabriel Adrián; Zwirner, Norberto Walter; Up-regulated expression of MICA on activated T lymphocytes involves Lck and Fyn kinases, and signaling through MEK1/ERK, p38 MAP kinase and calcineurin; Federation of American Societies for Experimental Biology; Journal of Leukocyte Biology; 73; 6; 1-6-2003; 815-8220741-5400CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1189/jlb.0602329/fullinfo:eu-repo/semantics/altIdentifier/url/10.1189/jlb.0602329info:eu-repo/semantics/altIdentifier/pmid/12773514info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:19:11Zoai:ri.conicet.gov.ar:11336/36414instacron: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 15:19:11.48CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Up-regulated expression of MICA on activated T lymphocytes involves Lck and Fyn kinases, and signaling through MEK1/ERK, p38 MAP kinase and calcineurin
title Up-regulated expression of MICA on activated T lymphocytes involves Lck and Fyn kinases, and signaling through MEK1/ERK, p38 MAP kinase and calcineurin
spellingShingle Up-regulated expression of MICA on activated T lymphocytes involves Lck and Fyn kinases, and signaling through MEK1/ERK, p38 MAP kinase and calcineurin
Molinero, Luciana Lorena
Major Histocompatibiblity Complex
Signaling Pathways
Nkg2d
Mica
title_short Up-regulated expression of MICA on activated T lymphocytes involves Lck and Fyn kinases, and signaling through MEK1/ERK, p38 MAP kinase and calcineurin
title_full Up-regulated expression of MICA on activated T lymphocytes involves Lck and Fyn kinases, and signaling through MEK1/ERK, p38 MAP kinase and calcineurin
title_fullStr Up-regulated expression of MICA on activated T lymphocytes involves Lck and Fyn kinases, and signaling through MEK1/ERK, p38 MAP kinase and calcineurin
title_full_unstemmed Up-regulated expression of MICA on activated T lymphocytes involves Lck and Fyn kinases, and signaling through MEK1/ERK, p38 MAP kinase and calcineurin
title_sort Up-regulated expression of MICA on activated T lymphocytes involves Lck and Fyn kinases, and signaling through MEK1/ERK, p38 MAP kinase and calcineurin
dc.creator.none.fl_str_mv Molinero, Luciana Lorena
Fuertes, Mercedes Beatriz
Fainboim, Leonardo
Rabinovich, Gabriel Adrián
Zwirner, Norberto Walter
author Molinero, Luciana Lorena
author_facet Molinero, Luciana Lorena
Fuertes, Mercedes Beatriz
Fainboim, Leonardo
Rabinovich, Gabriel Adrián
Zwirner, Norberto Walter
author_role author
author2 Fuertes, Mercedes Beatriz
Fainboim, Leonardo
Rabinovich, Gabriel Adrián
Zwirner, Norberto Walter
author2_role author
author
author
author
dc.subject.none.fl_str_mv Major Histocompatibiblity Complex
Signaling Pathways
Nkg2d
Mica
topic Major Histocompatibiblity Complex
Signaling Pathways
Nkg2d
Mica
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Major histocompatibility complex class I-related chain (MICA) is a cell stress-regulated molecule recognized by cytotoxic cells expressing the NKG2D molecule. MICA can be induced on T cells after CD3 or CD28 engagement. Here, we investigated the intracellular pathways leading to activation-induced expression of MICA. The Src kinase inhibitor PP1 inhibited up-regulated expression of MICA on anti-CD3-stimulated T cells. Downstream signaling routes involved mitogen-activated protein kinase (MAPK) kinase (MEK)1/extracellular signal-regulated kinase (ERK), p38 MAPK, and calcineurin, as MICA expression was prevented by U0126, SB202190, cyclosporin A, and FK506. Also, Lck and Fyn as well as MEK1/ERK and p38 MAPK were found to regulate MICA expression in anti-CD28/phorbol 12-myristate 13-acetate-stimulated T cells. Expression of MICA on activated T cells involved interleukin-2-dependent signaling routes triggered by Janus tyrosine kinases/signal transducer and activators of transcription and p70S6 kinase, as it could be inhibited by AG490 and rapamycin. This is the first demonstration of the intracellular pathways involved in activation-induced expression of MICA, which may reveal potential targets for immune intervention to modulate MICA expression in pathological disorders.
Fil: Molinero, Luciana Lorena. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Fuertes, Mercedes Beatriz. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Fainboim, Leonardo. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Rabinovich, Gabriel Adrián. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Zwirner, Norberto Walter. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
description Major histocompatibility complex class I-related chain (MICA) is a cell stress-regulated molecule recognized by cytotoxic cells expressing the NKG2D molecule. MICA can be induced on T cells after CD3 or CD28 engagement. Here, we investigated the intracellular pathways leading to activation-induced expression of MICA. The Src kinase inhibitor PP1 inhibited up-regulated expression of MICA on anti-CD3-stimulated T cells. Downstream signaling routes involved mitogen-activated protein kinase (MAPK) kinase (MEK)1/extracellular signal-regulated kinase (ERK), p38 MAPK, and calcineurin, as MICA expression was prevented by U0126, SB202190, cyclosporin A, and FK506. Also, Lck and Fyn as well as MEK1/ERK and p38 MAPK were found to regulate MICA expression in anti-CD28/phorbol 12-myristate 13-acetate-stimulated T cells. Expression of MICA on activated T cells involved interleukin-2-dependent signaling routes triggered by Janus tyrosine kinases/signal transducer and activators of transcription and p70S6 kinase, as it could be inhibited by AG490 and rapamycin. This is the first demonstration of the intracellular pathways involved in activation-induced expression of MICA, which may reveal potential targets for immune intervention to modulate MICA expression in pathological disorders.
publishDate 2003
dc.date.none.fl_str_mv 2003-06-01
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/11336/36414
Molinero, Luciana Lorena; Fuertes, Mercedes Beatriz; Fainboim, Leonardo; Rabinovich, Gabriel Adrián; Zwirner, Norberto Walter; Up-regulated expression of MICA on activated T lymphocytes involves Lck and Fyn kinases, and signaling through MEK1/ERK, p38 MAP kinase and calcineurin; Federation of American Societies for Experimental Biology; Journal of Leukocyte Biology; 73; 6; 1-6-2003; 815-822
0741-5400
CONICET Digital
CONICET
url http://hdl.handle.net/11336/36414
identifier_str_mv Molinero, Luciana Lorena; Fuertes, Mercedes Beatriz; Fainboim, Leonardo; Rabinovich, Gabriel Adrián; Zwirner, Norberto Walter; Up-regulated expression of MICA on activated T lymphocytes involves Lck and Fyn kinases, and signaling through MEK1/ERK, p38 MAP kinase and calcineurin; Federation of American Societies for Experimental Biology; Journal of Leukocyte Biology; 73; 6; 1-6-2003; 815-822
0741-5400
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1189/jlb.0602329/full
info:eu-repo/semantics/altIdentifier/url/10.1189/jlb.0602329
info:eu-repo/semantics/altIdentifier/pmid/12773514
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
application/pdf
dc.publisher.none.fl_str_mv Federation of American Societies for Experimental Biology
publisher.none.fl_str_mv Federation of American Societies for Experimental Biology
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 13.22299

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