Sam68 mediates leptin-stimulated growth by modulating leptin receptor signaling in human trophoblastic JEG-3 cells

Autores
Sánchez Jiménez, F.; Pérez Pérez, A.; González Yanes, C.; Varone, Cecilia Laura; Sánchez Margalet, V.
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background Sam68, a member of the signal transduction and activation of RNA metabolism (STAR) family of RNA-binding proteins, has been previously implicated as an adaptor molecule in different signaling systems, including leptin receptor (LEPR) signaling. LEPR activation is known to stimulate JAK-STAT, MAPK and PI3K signaling pathways, thus mediating the biological effects of leptin in different cell types, including trophoblastic cells. We have recently found that leptin stimulation also promotes the overexpression and tyrosine phosphorylation of Sam68 in human trophoblastic JEG-3 cells, suggesting a role for Sam68 in leptin signaling and action in these cells. In the present work, we have studied the participation of Sam68 in the main signaling pathways activated by LEPR to increase growth and proliferation in trophoblastic JEG-3 cells. Methods We used an antisense strategy to down-regulate Sam68 expression in these cells, and we studied LEPR signaling by immunoprecipitation and poly-U affinity precipitation and by analyzing phosphorylation levels of signaling proteins by immunoblot. The effect of leptin on protein synthesis and proliferation was studied by 3[H]-leucine and 3[H]-thymidine incorporation. Results Sam68 knockdown impaired leptin activation of JAK-STAT, PI3K and MAPK signaling pathways in JEG-3 cells. We have also found that leptin-stimulated Sam68 tyrosine phosphorylation is dependent on JAK-2 activity, since the pharmacological inhibitor AG490 prevents the phosphorylation of Sam68 in JEG-3 cells. Finally, the trophic and proliferative effect of leptin in trophoblastic cells is dependent on Sam68 expression, since its down-regulation impaired the leptin-stimulated DNA and protein synthesis. Conclusions These data demonstrate that Sam68 participates in the main signaling pathways of LEPR to mediate the trophic and proliferative effect of leptin in human trophoblastic cells.
Fil: Sánchez Jiménez, F.. Universidad de Sevilla; España
Fil: Pérez Pérez, A.. Universidad de Sevilla; España
Fil: González Yanes, C.. Universidad de Sevilla; España
Fil: Varone, Cecilia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Sánchez Margalet, V.. Universidad de Sevilla; España
Materia
LEPR SIGNALING
LEPTIN
PLACENTA
SAM68
TROPHOBLAST
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:11336/95901

id CONICETDig_731bcc808c9bd8a250108a230fb36730
oai_identifier_str oai:ri.conicet.gov.ar:11336/95901
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Sam68 mediates leptin-stimulated growth by modulating leptin receptor signaling in human trophoblastic JEG-3 cellsSánchez Jiménez, F.Pérez Pérez, A.González Yanes, C.Varone, Cecilia LauraSánchez Margalet, V.LEPR SIGNALINGLEPTINPLACENTASAM68TROPHOBLASThttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background Sam68, a member of the signal transduction and activation of RNA metabolism (STAR) family of RNA-binding proteins, has been previously implicated as an adaptor molecule in different signaling systems, including leptin receptor (LEPR) signaling. LEPR activation is known to stimulate JAK-STAT, MAPK and PI3K signaling pathways, thus mediating the biological effects of leptin in different cell types, including trophoblastic cells. We have recently found that leptin stimulation also promotes the overexpression and tyrosine phosphorylation of Sam68 in human trophoblastic JEG-3 cells, suggesting a role for Sam68 in leptin signaling and action in these cells. In the present work, we have studied the participation of Sam68 in the main signaling pathways activated by LEPR to increase growth and proliferation in trophoblastic JEG-3 cells. Methods We used an antisense strategy to down-regulate Sam68 expression in these cells, and we studied LEPR signaling by immunoprecipitation and poly-U affinity precipitation and by analyzing phosphorylation levels of signaling proteins by immunoblot. The effect of leptin on protein synthesis and proliferation was studied by 3[H]-leucine and 3[H]-thymidine incorporation. Results Sam68 knockdown impaired leptin activation of JAK-STAT, PI3K and MAPK signaling pathways in JEG-3 cells. We have also found that leptin-stimulated Sam68 tyrosine phosphorylation is dependent on JAK-2 activity, since the pharmacological inhibitor AG490 prevents the phosphorylation of Sam68 in JEG-3 cells. Finally, the trophic and proliferative effect of leptin in trophoblastic cells is dependent on Sam68 expression, since its down-regulation impaired the leptin-stimulated DNA and protein synthesis. Conclusions These data demonstrate that Sam68 participates in the main signaling pathways of LEPR to mediate the trophic and proliferative effect of leptin in human trophoblastic cells.Fil: Sánchez Jiménez, F.. Universidad de Sevilla; EspañaFil: Pérez Pérez, A.. Universidad de Sevilla; EspañaFil: González Yanes, C.. Universidad de Sevilla; EspañaFil: Varone, Cecilia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Sánchez Margalet, V.. Universidad de Sevilla; EspañaOxford University Press2011-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/95901Sánchez Jiménez, F.; Pérez Pérez, A.; González Yanes, C.; Varone, Cecilia Laura; Sánchez Margalet, V.; Sam68 mediates leptin-stimulated growth by modulating leptin receptor signaling in human trophoblastic JEG-3 cells; Oxford University Press; Human Reproduction; 26; 9; 6-2011; 2306-23150268-1161CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/humrep/article/26/9/2306/720090info:eu-repo/semantics/altIdentifier/doi/10.1093/humrep/der187info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:44:27Zoai:ri.conicet.gov.ar:11336/95901instacron: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 09:44:28.12CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Sam68 mediates leptin-stimulated growth by modulating leptin receptor signaling in human trophoblastic JEG-3 cells
title Sam68 mediates leptin-stimulated growth by modulating leptin receptor signaling in human trophoblastic JEG-3 cells
spellingShingle Sam68 mediates leptin-stimulated growth by modulating leptin receptor signaling in human trophoblastic JEG-3 cells
Sánchez Jiménez, F.
LEPR SIGNALING
LEPTIN
PLACENTA
SAM68
TROPHOBLAST
title_short Sam68 mediates leptin-stimulated growth by modulating leptin receptor signaling in human trophoblastic JEG-3 cells
title_full Sam68 mediates leptin-stimulated growth by modulating leptin receptor signaling in human trophoblastic JEG-3 cells
title_fullStr Sam68 mediates leptin-stimulated growth by modulating leptin receptor signaling in human trophoblastic JEG-3 cells
title_full_unstemmed Sam68 mediates leptin-stimulated growth by modulating leptin receptor signaling in human trophoblastic JEG-3 cells
title_sort Sam68 mediates leptin-stimulated growth by modulating leptin receptor signaling in human trophoblastic JEG-3 cells
dc.creator.none.fl_str_mv Sánchez Jiménez, F.
Pérez Pérez, A.
González Yanes, C.
Varone, Cecilia Laura
Sánchez Margalet, V.
author Sánchez Jiménez, F.
author_facet Sánchez Jiménez, F.
Pérez Pérez, A.
González Yanes, C.
Varone, Cecilia Laura
Sánchez Margalet, V.
author_role author
author2 Pérez Pérez, A.
González Yanes, C.
Varone, Cecilia Laura
Sánchez Margalet, V.
author2_role author
author
author
author
dc.subject.none.fl_str_mv LEPR SIGNALING
LEPTIN
PLACENTA
SAM68
TROPHOBLAST
topic LEPR SIGNALING
LEPTIN
PLACENTA
SAM68
TROPHOBLAST
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background Sam68, a member of the signal transduction and activation of RNA metabolism (STAR) family of RNA-binding proteins, has been previously implicated as an adaptor molecule in different signaling systems, including leptin receptor (LEPR) signaling. LEPR activation is known to stimulate JAK-STAT, MAPK and PI3K signaling pathways, thus mediating the biological effects of leptin in different cell types, including trophoblastic cells. We have recently found that leptin stimulation also promotes the overexpression and tyrosine phosphorylation of Sam68 in human trophoblastic JEG-3 cells, suggesting a role for Sam68 in leptin signaling and action in these cells. In the present work, we have studied the participation of Sam68 in the main signaling pathways activated by LEPR to increase growth and proliferation in trophoblastic JEG-3 cells. Methods We used an antisense strategy to down-regulate Sam68 expression in these cells, and we studied LEPR signaling by immunoprecipitation and poly-U affinity precipitation and by analyzing phosphorylation levels of signaling proteins by immunoblot. The effect of leptin on protein synthesis and proliferation was studied by 3[H]-leucine and 3[H]-thymidine incorporation. Results Sam68 knockdown impaired leptin activation of JAK-STAT, PI3K and MAPK signaling pathways in JEG-3 cells. We have also found that leptin-stimulated Sam68 tyrosine phosphorylation is dependent on JAK-2 activity, since the pharmacological inhibitor AG490 prevents the phosphorylation of Sam68 in JEG-3 cells. Finally, the trophic and proliferative effect of leptin in trophoblastic cells is dependent on Sam68 expression, since its down-regulation impaired the leptin-stimulated DNA and protein synthesis. Conclusions These data demonstrate that Sam68 participates in the main signaling pathways of LEPR to mediate the trophic and proliferative effect of leptin in human trophoblastic cells.
Fil: Sánchez Jiménez, F.. Universidad de Sevilla; España
Fil: Pérez Pérez, A.. Universidad de Sevilla; España
Fil: González Yanes, C.. Universidad de Sevilla; España
Fil: Varone, Cecilia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Sánchez Margalet, V.. Universidad de Sevilla; España
description Background Sam68, a member of the signal transduction and activation of RNA metabolism (STAR) family of RNA-binding proteins, has been previously implicated as an adaptor molecule in different signaling systems, including leptin receptor (LEPR) signaling. LEPR activation is known to stimulate JAK-STAT, MAPK and PI3K signaling pathways, thus mediating the biological effects of leptin in different cell types, including trophoblastic cells. We have recently found that leptin stimulation also promotes the overexpression and tyrosine phosphorylation of Sam68 in human trophoblastic JEG-3 cells, suggesting a role for Sam68 in leptin signaling and action in these cells. In the present work, we have studied the participation of Sam68 in the main signaling pathways activated by LEPR to increase growth and proliferation in trophoblastic JEG-3 cells. Methods We used an antisense strategy to down-regulate Sam68 expression in these cells, and we studied LEPR signaling by immunoprecipitation and poly-U affinity precipitation and by analyzing phosphorylation levels of signaling proteins by immunoblot. The effect of leptin on protein synthesis and proliferation was studied by 3[H]-leucine and 3[H]-thymidine incorporation. Results Sam68 knockdown impaired leptin activation of JAK-STAT, PI3K and MAPK signaling pathways in JEG-3 cells. We have also found that leptin-stimulated Sam68 tyrosine phosphorylation is dependent on JAK-2 activity, since the pharmacological inhibitor AG490 prevents the phosphorylation of Sam68 in JEG-3 cells. Finally, the trophic and proliferative effect of leptin in trophoblastic cells is dependent on Sam68 expression, since its down-regulation impaired the leptin-stimulated DNA and protein synthesis. Conclusions These data demonstrate that Sam68 participates in the main signaling pathways of LEPR to mediate the trophic and proliferative effect of leptin in human trophoblastic cells.
publishDate 2011
dc.date.none.fl_str_mv 2011-06
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/11336/95901
Sánchez Jiménez, F.; Pérez Pérez, A.; González Yanes, C.; Varone, Cecilia Laura; Sánchez Margalet, V.; Sam68 mediates leptin-stimulated growth by modulating leptin receptor signaling in human trophoblastic JEG-3 cells; Oxford University Press; Human Reproduction; 26; 9; 6-2011; 2306-2315
0268-1161
CONICET Digital
CONICET
url http://hdl.handle.net/11336/95901
identifier_str_mv Sánchez Jiménez, F.; Pérez Pérez, A.; González Yanes, C.; Varone, Cecilia Laura; Sánchez Margalet, V.; Sam68 mediates leptin-stimulated growth by modulating leptin receptor signaling in human trophoblastic JEG-3 cells; Oxford University Press; Human Reproduction; 26; 9; 6-2011; 2306-2315
0268-1161
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/humrep/article/26/9/2306/720090
info:eu-repo/semantics/altIdentifier/doi/10.1093/humrep/der187
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
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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
_version_ 1842268667773976576
score 13.13397