The sarcolemmal calcium pump inhibits the calcineurin/nuclear factor of activated T-cell pathway via interaction with the calcineurin A catalytic subunit

The calcineurin/nuclear factor of activated T-cell (NFAT) pathway represents a crucial transducer of cellular function. There is increasing evidence placing the sarcolemmal calcium pump, or plasma membrane calcium/calmodulin ATPase pump (PMCA), as a potential modulator of signal transduction pathway...

Descripción completa

Detalles Bibliográficos
Autores: Buch, Mamta H., Pickard, Adam, Rodríguez, Antonio, Gillies, Sheona, Maass, Alexander H., Emerson, Michael, Cartwright, Elizabeth J., Williams, Judith C., Oceandy, Delvac, Redondo, Juan M., Neyses, Ludwig, Armesilla, Angel L.
Tipo de recurso: artículo
Fecha de publicación:2005
País:España
Institución:Universidad Camilo José Cela (UCJC)
Repositorio:Depósito Digital e-UCJC
OAI Identifier:oai:repositorio.ucjc.edu:20.500.12020/1852
Acceso en línea:http://hdl.handle.net/20.500.12020/1852
https://doi.org/10.1074/jbc.m501326200
Access Level:acceso abierto
Palabra clave:Biología Celular y Molecular
Ciencias Biomédicas
PMCA4
Calcineurin
Protein interaction
Signal transduction
32 Ciencias Médicas
id ES_ce58974f27da2efa41b9cb65cd5f7901
oai_identifier_str oai:repositorio.ucjc.edu:20.500.12020/1852
network_acronym_str ES
network_name_str España
repository_id_str
spelling The sarcolemmal calcium pump inhibits the calcineurin/nuclear factor of activated T-cell pathway via interaction with the calcineurin A catalytic subunitInhibition of Calcineurin by PMCABuch, Mamta H.Pickard, AdamRodríguez, AntonioGillies, SheonaMaass, Alexander H.Emerson, MichaelCartwright, Elizabeth J.Williams, Judith C.Oceandy, DelvacRedondo, Juan M.Neyses, LudwigArmesilla, Angel L.Biología Celular y MolecularCiencias BiomédicasPMCA4CalcineurinProtein interactionSignal transduction32 Ciencias MédicasThe calcineurin/nuclear factor of activated T-cell (NFAT) pathway represents a crucial transducer of cellular function. There is increasing evidence placing the sarcolemmal calcium pump, or plasma membrane calcium/calmodulin ATPase pump (PMCA), as a potential modulator of signal transduction pathways. We demonstrate a novel interaction between PMCA and the calcium/calmodulin-dependent phosphatase, calcineurin, in mammalian cells. The interaction domains were located to the catalytic domain of PMCA4b and the catalytic domain of the calcineurin A subunit. Endogenous calcineurin activity, assessed by measuring the transcriptional activity of its best characterized substrate, NFAT, was significantly inhibited by 60% in the presence of ectopic PMCA4b. This inhibition was notably reversed by the co-expression of the PMCA4b interaction domain, demonstrating the functional significance of this interaction. PMCA4b was, however, unable to confer its inhibitory effect in the presence of a calcium/calmodulin-independent constitutively active mutant calcineurin A suggesting a calcium/calmodulin-dependent mechanism. The modulatory function of PMCA4b is further supported by the observation that endogenous calcineurin moves from the cytoplasm to the plasma membrane when PMCA4b is overexpressed. We suggest recruitment by PMCA4b of calcineurin to a low calcium environment as a possible explanation for these findings. In summary, our results offer strong evidence for a novel functional interaction between PMCA and calcineurin, suggesting a role for PMCA as a negative modulator of calcineurin-mediated signaling pathways in mammalian cells. This study reinforces the emerging role of PMCA as a molecular organizer and regulator of signaling transduction pathways.Elsevier2005info:eu-repo/semantics/articlehttp://hdl.handle.net/20.500.12020/1852https://doi.org/10.1074/jbc.m501326200reponame:Depósito Digital e-UCJCinstname:Universidad Camilo José Cela (UCJC)Inglésinfo:eu-repo/semantics/openAccessoai:repositorio.ucjc.edu:20.500.12020/18522026-05-27T07:36:51Z
dc.title.none.fl_str_mv The sarcolemmal calcium pump inhibits the calcineurin/nuclear factor of activated T-cell pathway via interaction with the calcineurin A catalytic subunit
Inhibition of Calcineurin by PMCA
title The sarcolemmal calcium pump inhibits the calcineurin/nuclear factor of activated T-cell pathway via interaction with the calcineurin A catalytic subunit
spellingShingle The sarcolemmal calcium pump inhibits the calcineurin/nuclear factor of activated T-cell pathway via interaction with the calcineurin A catalytic subunit
Buch, Mamta H.
Biología Celular y Molecular
Ciencias Biomédicas
PMCA4
Calcineurin
Protein interaction
Signal transduction
32 Ciencias Médicas
title_short The sarcolemmal calcium pump inhibits the calcineurin/nuclear factor of activated T-cell pathway via interaction with the calcineurin A catalytic subunit
title_full The sarcolemmal calcium pump inhibits the calcineurin/nuclear factor of activated T-cell pathway via interaction with the calcineurin A catalytic subunit
title_fullStr The sarcolemmal calcium pump inhibits the calcineurin/nuclear factor of activated T-cell pathway via interaction with the calcineurin A catalytic subunit
title_full_unstemmed The sarcolemmal calcium pump inhibits the calcineurin/nuclear factor of activated T-cell pathway via interaction with the calcineurin A catalytic subunit
title_sort The sarcolemmal calcium pump inhibits the calcineurin/nuclear factor of activated T-cell pathway via interaction with the calcineurin A catalytic subunit
dc.creator.none.fl_str_mv Buch, Mamta H.
Pickard, Adam
Rodríguez, Antonio
Gillies, Sheona
Maass, Alexander H.
Emerson, Michael
Cartwright, Elizabeth J.
Williams, Judith C.
Oceandy, Delvac
Redondo, Juan M.
Neyses, Ludwig
Armesilla, Angel L.
author Buch, Mamta H.
author_facet Buch, Mamta H.
Pickard, Adam
Rodríguez, Antonio
Gillies, Sheona
Maass, Alexander H.
Emerson, Michael
Cartwright, Elizabeth J.
Williams, Judith C.
Oceandy, Delvac
Redondo, Juan M.
Neyses, Ludwig
Armesilla, Angel L.
author_role author
author2 Pickard, Adam
Rodríguez, Antonio
Gillies, Sheona
Maass, Alexander H.
Emerson, Michael
Cartwright, Elizabeth J.
Williams, Judith C.
Oceandy, Delvac
Redondo, Juan M.
Neyses, Ludwig
Armesilla, Angel L.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Biología Celular y Molecular
Ciencias Biomédicas
PMCA4
Calcineurin
Protein interaction
Signal transduction
32 Ciencias Médicas
topic Biología Celular y Molecular
Ciencias Biomédicas
PMCA4
Calcineurin
Protein interaction
Signal transduction
32 Ciencias Médicas
description The calcineurin/nuclear factor of activated T-cell (NFAT) pathway represents a crucial transducer of cellular function. There is increasing evidence placing the sarcolemmal calcium pump, or plasma membrane calcium/calmodulin ATPase pump (PMCA), as a potential modulator of signal transduction pathways. We demonstrate a novel interaction between PMCA and the calcium/calmodulin-dependent phosphatase, calcineurin, in mammalian cells. The interaction domains were located to the catalytic domain of PMCA4b and the catalytic domain of the calcineurin A subunit. Endogenous calcineurin activity, assessed by measuring the transcriptional activity of its best characterized substrate, NFAT, was significantly inhibited by 60% in the presence of ectopic PMCA4b. This inhibition was notably reversed by the co-expression of the PMCA4b interaction domain, demonstrating the functional significance of this interaction. PMCA4b was, however, unable to confer its inhibitory effect in the presence of a calcium/calmodulin-independent constitutively active mutant calcineurin A suggesting a calcium/calmodulin-dependent mechanism. The modulatory function of PMCA4b is further supported by the observation that endogenous calcineurin moves from the cytoplasm to the plasma membrane when PMCA4b is overexpressed. We suggest recruitment by PMCA4b of calcineurin to a low calcium environment as a possible explanation for these findings. In summary, our results offer strong evidence for a novel functional interaction between PMCA and calcineurin, suggesting a role for PMCA as a negative modulator of calcineurin-mediated signaling pathways in mammalian cells. This study reinforces the emerging role of PMCA as a molecular organizer and regulator of signaling transduction pathways.
publishDate 2005
dc.date.none.fl_str_mv 2005
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12020/1852
https://doi.org/10.1074/jbc.m501326200
url http://hdl.handle.net/20.500.12020/1852
https://doi.org/10.1074/jbc.m501326200
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Depósito Digital e-UCJC
instname:Universidad Camilo José Cela (UCJC)
instname_str Universidad Camilo José Cela (UCJC)
reponame_str Depósito Digital e-UCJC
collection Depósito Digital e-UCJC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869419982710898688
score 15,81155

Similares en LA Referencia