AT 2 receptors recruit c-Src, SHP-1 and FAK upon activation by Ang II in PND15 rat hindbrain

Autores
Seguin, Leonardo Roque; Villarreal, Rodrigo Sebastian; Ciuffo, Gladys Maria
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The functional role of AT 2 receptors is unclear and it activates unconventional signaling pathways, which in general do not involve a classical activation of a G-protein. In the present study, we aimed to investigate the transduction mechanism of AT 2 Ang II receptors in PND15 rat hindbrain membrane preparations, which represents a physiological developmental condition. To determine whether Ang II AT 2 receptors induced association to SHP-1 in rat hindbrain, co-immunoprecipitation assays were performed. Stimulation of Ang II AT 2 receptors induced both a transient tyr-phosphorylation and activation of SHP-1. The possible participation of c-Src in Ang II-mediated SHP-1 activation, we demonstrated by recruitment of c-Src in immunocomplexes obtained with anti AT 2 or anti-SHP-1 antibodies. The association of SHP-1 to c-Src was inhibited by PD123319 and the c-Src inhibitor PP2. Similarly, SHP-1 activity determined in AT 2-immunocomplexes was inhibited by PD123319 and the c-Src inhibitor PP2. Following stimulation with Ang II, AT 2 receptors recruit c-Src, which was responsible for SHP-1 tyr-phosphorylation and activation. Since AT 2 receptors are involved in neuron migration, we tested the presence of FAK in immunocomplexes. Surprisingly, AT 2-immunocomplexes contained mainly the 85 kDa fragment of FAK. Besides, p125FAK associated to SHP-1. In summary, we demonstrated the presence of an active signal transduction mechanism in PND15 rat hindbrain, a developmental stage critical for cerebellar development. In this model, we showed a complex containing AT 2/SHP-1/c-Src/p85FAK, suggesting a potential role of Ang II AT 2 receptors in cerebellar development and neuronal differentiation.
Fil: Seguin, Leonardo Roque. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Villarreal, Rodrigo Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Ciuffo, Gladys Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Materia
AT 2 RECEPTORS
FOCAL ADHESION KINASE
HINDBRAIN DEVELOPMENT
SHP-1/C-SRC INTERACTION
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:11336/125889
Acceder
id CONICETDig_a28ab9038d81496f03385a5dcb29b762
oai_identifier_str oai:ri.conicet.gov.ar:11336/125889
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling AT 2 receptors recruit c-Src, SHP-1 and FAK upon activation by Ang II in PND15 rat hindbrainSeguin, Leonardo RoqueVillarreal, Rodrigo SebastianCiuffo, Gladys MariaAT 2 RECEPTORSFOCAL ADHESION KINASEHINDBRAIN DEVELOPMENTSHP-1/C-SRC INTERACTIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The functional role of AT 2 receptors is unclear and it activates unconventional signaling pathways, which in general do not involve a classical activation of a G-protein. In the present study, we aimed to investigate the transduction mechanism of AT 2 Ang II receptors in PND15 rat hindbrain membrane preparations, which represents a physiological developmental condition. To determine whether Ang II AT 2 receptors induced association to SHP-1 in rat hindbrain, co-immunoprecipitation assays were performed. Stimulation of Ang II AT 2 receptors induced both a transient tyr-phosphorylation and activation of SHP-1. The possible participation of c-Src in Ang II-mediated SHP-1 activation, we demonstrated by recruitment of c-Src in immunocomplexes obtained with anti AT 2 or anti-SHP-1 antibodies. The association of SHP-1 to c-Src was inhibited by PD123319 and the c-Src inhibitor PP2. Similarly, SHP-1 activity determined in AT 2-immunocomplexes was inhibited by PD123319 and the c-Src inhibitor PP2. Following stimulation with Ang II, AT 2 receptors recruit c-Src, which was responsible for SHP-1 tyr-phosphorylation and activation. Since AT 2 receptors are involved in neuron migration, we tested the presence of FAK in immunocomplexes. Surprisingly, AT 2-immunocomplexes contained mainly the 85 kDa fragment of FAK. Besides, p125FAK associated to SHP-1. In summary, we demonstrated the presence of an active signal transduction mechanism in PND15 rat hindbrain, a developmental stage critical for cerebellar development. In this model, we showed a complex containing AT 2/SHP-1/c-Src/p85FAK, suggesting a potential role of Ang II AT 2 receptors in cerebellar development and neuronal differentiation.Fil: Seguin, Leonardo Roque. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Villarreal, Rodrigo Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Ciuffo, Gladys Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaPergamon-Elsevier Science Ltd2012-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/125889Seguin, Leonardo Roque; Villarreal, Rodrigo Sebastian; Ciuffo, Gladys Maria; AT 2 receptors recruit c-Src, SHP-1 and FAK upon activation by Ang II in PND15 rat hindbrain; Pergamon-Elsevier Science Ltd; Neurochemistry International; 60; 2; 1-2012; 199-2070197-0186CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0197018611003731info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neuint.2011.11.008info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:35:21Zoai:ri.conicet.gov.ar:11336/125889instacron: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:34982025-09-29 09:35:21.973CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv AT 2 receptors recruit c-Src, SHP-1 and FAK upon activation by Ang II in PND15 rat hindbrain
title AT 2 receptors recruit c-Src, SHP-1 and FAK upon activation by Ang II in PND15 rat hindbrain
spellingShingle AT 2 receptors recruit c-Src, SHP-1 and FAK upon activation by Ang II in PND15 rat hindbrain
Seguin, Leonardo Roque
AT 2 RECEPTORS
FOCAL ADHESION KINASE
HINDBRAIN DEVELOPMENT
SHP-1/C-SRC INTERACTION
title_short AT 2 receptors recruit c-Src, SHP-1 and FAK upon activation by Ang II in PND15 rat hindbrain
title_full AT 2 receptors recruit c-Src, SHP-1 and FAK upon activation by Ang II in PND15 rat hindbrain
title_fullStr AT 2 receptors recruit c-Src, SHP-1 and FAK upon activation by Ang II in PND15 rat hindbrain
title_full_unstemmed AT 2 receptors recruit c-Src, SHP-1 and FAK upon activation by Ang II in PND15 rat hindbrain
title_sort AT 2 receptors recruit c-Src, SHP-1 and FAK upon activation by Ang II in PND15 rat hindbrain
dc.creator.none.fl_str_mv Seguin, Leonardo Roque
Villarreal, Rodrigo Sebastian
Ciuffo, Gladys Maria
author Seguin, Leonardo Roque
author_facet Seguin, Leonardo Roque
Villarreal, Rodrigo Sebastian
Ciuffo, Gladys Maria
author_role author
author2 Villarreal, Rodrigo Sebastian
Ciuffo, Gladys Maria
author2_role author
author
dc.subject.none.fl_str_mv AT 2 RECEPTORS
FOCAL ADHESION KINASE
HINDBRAIN DEVELOPMENT
SHP-1/C-SRC INTERACTION
topic AT 2 RECEPTORS
FOCAL ADHESION KINASE
HINDBRAIN DEVELOPMENT
SHP-1/C-SRC INTERACTION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The functional role of AT 2 receptors is unclear and it activates unconventional signaling pathways, which in general do not involve a classical activation of a G-protein. In the present study, we aimed to investigate the transduction mechanism of AT 2 Ang II receptors in PND15 rat hindbrain membrane preparations, which represents a physiological developmental condition. To determine whether Ang II AT 2 receptors induced association to SHP-1 in rat hindbrain, co-immunoprecipitation assays were performed. Stimulation of Ang II AT 2 receptors induced both a transient tyr-phosphorylation and activation of SHP-1. The possible participation of c-Src in Ang II-mediated SHP-1 activation, we demonstrated by recruitment of c-Src in immunocomplexes obtained with anti AT 2 or anti-SHP-1 antibodies. The association of SHP-1 to c-Src was inhibited by PD123319 and the c-Src inhibitor PP2. Similarly, SHP-1 activity determined in AT 2-immunocomplexes was inhibited by PD123319 and the c-Src inhibitor PP2. Following stimulation with Ang II, AT 2 receptors recruit c-Src, which was responsible for SHP-1 tyr-phosphorylation and activation. Since AT 2 receptors are involved in neuron migration, we tested the presence of FAK in immunocomplexes. Surprisingly, AT 2-immunocomplexes contained mainly the 85 kDa fragment of FAK. Besides, p125FAK associated to SHP-1. In summary, we demonstrated the presence of an active signal transduction mechanism in PND15 rat hindbrain, a developmental stage critical for cerebellar development. In this model, we showed a complex containing AT 2/SHP-1/c-Src/p85FAK, suggesting a potential role of Ang II AT 2 receptors in cerebellar development and neuronal differentiation.
Fil: Seguin, Leonardo Roque. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Villarreal, Rodrigo Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Ciuffo, Gladys Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
description The functional role of AT 2 receptors is unclear and it activates unconventional signaling pathways, which in general do not involve a classical activation of a G-protein. In the present study, we aimed to investigate the transduction mechanism of AT 2 Ang II receptors in PND15 rat hindbrain membrane preparations, which represents a physiological developmental condition. To determine whether Ang II AT 2 receptors induced association to SHP-1 in rat hindbrain, co-immunoprecipitation assays were performed. Stimulation of Ang II AT 2 receptors induced both a transient tyr-phosphorylation and activation of SHP-1. The possible participation of c-Src in Ang II-mediated SHP-1 activation, we demonstrated by recruitment of c-Src in immunocomplexes obtained with anti AT 2 or anti-SHP-1 antibodies. The association of SHP-1 to c-Src was inhibited by PD123319 and the c-Src inhibitor PP2. Similarly, SHP-1 activity determined in AT 2-immunocomplexes was inhibited by PD123319 and the c-Src inhibitor PP2. Following stimulation with Ang II, AT 2 receptors recruit c-Src, which was responsible for SHP-1 tyr-phosphorylation and activation. Since AT 2 receptors are involved in neuron migration, we tested the presence of FAK in immunocomplexes. Surprisingly, AT 2-immunocomplexes contained mainly the 85 kDa fragment of FAK. Besides, p125FAK associated to SHP-1. In summary, we demonstrated the presence of an active signal transduction mechanism in PND15 rat hindbrain, a developmental stage critical for cerebellar development. In this model, we showed a complex containing AT 2/SHP-1/c-Src/p85FAK, suggesting a potential role of Ang II AT 2 receptors in cerebellar development and neuronal differentiation.
publishDate 2012
dc.date.none.fl_str_mv 2012-01
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/11336/125889
Seguin, Leonardo Roque; Villarreal, Rodrigo Sebastian; Ciuffo, Gladys Maria; AT 2 receptors recruit c-Src, SHP-1 and FAK upon activation by Ang II in PND15 rat hindbrain; Pergamon-Elsevier Science Ltd; Neurochemistry International; 60; 2; 1-2012; 199-207
0197-0186
CONICET Digital
CONICET
url http://hdl.handle.net/11336/125889
identifier_str_mv Seguin, Leonardo Roque; Villarreal, Rodrigo Sebastian; Ciuffo, Gladys Maria; AT 2 receptors recruit c-Src, SHP-1 and FAK upon activation by Ang II in PND15 rat hindbrain; Pergamon-Elsevier Science Ltd; Neurochemistry International; 60; 2; 1-2012; 199-207
0197-0186
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://www.sciencedirect.com/science/article/abs/pii/S0197018611003731
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neuint.2011.11.008
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
dc.publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
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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