Heterotrimeric Gi Proteins link Hedgehog signaling to activation of Rho small GTPases to promote fibroblast migration

Autores
Polizio, Ariel Héctor; Chinchilla, Pilar; Chen, Xiaole; Kim, Sangbumn; Manning, David R.; Riobo, Natalia A.
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Evidence supporting the functionality of Smoothened (SMO), an essential transducer in most pathways engaged by Hedgehog (Hh), as a Gi-coupled receptor contrasts with the lack of an apparently consistent requirement for Gi in Hh signal transduction. In the present study, we sought to evaluate the role of SMO-Gi coupling in fibroblast migration induced by Sonic Hedgehog (Shh). Our results demonstrate an absolute requirement for Gi in Shh-induced fibroblast migration. We found that Shh acutely stimulates the small Rho GTPases Rac1 and RhoA via SMO through a Gi protein- and PI3K-dependent mechanism, and that these are required for cell migration. These responses were independent of transcription by Gli and of the C-terminal domain of SMO, as we show using a combination of molecular and genetic tools. Our findings provide a mechanistic model for fibroblast migration in response to Shh and underscore the role of SMO-Gi coupling in non-canonical Hh signaling.
Fil: Polizio, Ariel Héctor. Thomas Jefferson University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Chinchilla, Pilar. Thomas Jefferson University; Estados Unidos
Fil: Chen, Xiaole. Thomas Jefferson University; Estados Unidos
Fil: Kim, Sangbumn. Thomas Jefferson University; Estados Unidos
Fil: Manning, David R.. University Of Pennsylvania; Estados Unidos
Fil: Riobo, Natalia A.. Thomas Jefferson University; Estados Unidos
Materia
Sonic HEDGEHOG
migration
cancer
signal pathways
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:11336/13181
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/13181
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Heterotrimeric Gi Proteins link Hedgehog signaling to activation of Rho small GTPases to promote fibroblast migrationPolizio, Ariel HéctorChinchilla, PilarChen, XiaoleKim, SangbumnManning, David R.Riobo, Natalia A.Sonic HEDGEHOGmigrationcancersignal pathwayshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Evidence supporting the functionality of Smoothened (SMO), an essential transducer in most pathways engaged by Hedgehog (Hh), as a Gi-coupled receptor contrasts with the lack of an apparently consistent requirement for Gi in Hh signal transduction. In the present study, we sought to evaluate the role of SMO-Gi coupling in fibroblast migration induced by Sonic Hedgehog (Shh). Our results demonstrate an absolute requirement for Gi in Shh-induced fibroblast migration. We found that Shh acutely stimulates the small Rho GTPases Rac1 and RhoA via SMO through a Gi protein- and PI3K-dependent mechanism, and that these are required for cell migration. These responses were independent of transcription by Gli and of the C-terminal domain of SMO, as we show using a combination of molecular and genetic tools. Our findings provide a mechanistic model for fibroblast migration in response to Shh and underscore the role of SMO-Gi coupling in non-canonical Hh signaling.Fil: Polizio, Ariel Héctor. Thomas Jefferson University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Chinchilla, Pilar. Thomas Jefferson University; Estados UnidosFil: Chen, Xiaole. Thomas Jefferson University; Estados UnidosFil: Kim, Sangbumn. Thomas Jefferson University; Estados UnidosFil: Manning, David R.. University Of Pennsylvania; Estados UnidosFil: Riobo, Natalia A.. Thomas Jefferson University; Estados UnidosAmerican Society For Biochemistry And Molecular Biology2011-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/13181Polizio, Ariel Héctor; Chinchilla, Pilar; Chen, Xiaole; Kim, Sangbumn; Manning, David R.; et al.; Heterotrimeric Gi Proteins link Hedgehog signaling to activation of Rho small GTPases to promote fibroblast migration; American Society For Biochemistry And Molecular Biology; Journal Of Biological Chemistry; 286; 7-2011; 19589-195960021-9258enginfo:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/286/22/19589.longinfo:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M110.197111info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3103338/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:41Zoai:ri.conicet.gov.ar:11336/13181instacron: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 09:51:41.481CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Heterotrimeric Gi Proteins link Hedgehog signaling to activation of Rho small GTPases to promote fibroblast migration
title Heterotrimeric Gi Proteins link Hedgehog signaling to activation of Rho small GTPases to promote fibroblast migration
spellingShingle Heterotrimeric Gi Proteins link Hedgehog signaling to activation of Rho small GTPases to promote fibroblast migration
Polizio, Ariel Héctor
Sonic HEDGEHOG
migration
cancer
signal pathways
title_short Heterotrimeric Gi Proteins link Hedgehog signaling to activation of Rho small GTPases to promote fibroblast migration
title_full Heterotrimeric Gi Proteins link Hedgehog signaling to activation of Rho small GTPases to promote fibroblast migration
title_fullStr Heterotrimeric Gi Proteins link Hedgehog signaling to activation of Rho small GTPases to promote fibroblast migration
title_full_unstemmed Heterotrimeric Gi Proteins link Hedgehog signaling to activation of Rho small GTPases to promote fibroblast migration
title_sort Heterotrimeric Gi Proteins link Hedgehog signaling to activation of Rho small GTPases to promote fibroblast migration
dc.creator.none.fl_str_mv Polizio, Ariel Héctor
Chinchilla, Pilar
Chen, Xiaole
Kim, Sangbumn
Manning, David R.
Riobo, Natalia A.
author Polizio, Ariel Héctor
author_facet Polizio, Ariel Héctor
Chinchilla, Pilar
Chen, Xiaole
Kim, Sangbumn
Manning, David R.
Riobo, Natalia A.
author_role author
author2 Chinchilla, Pilar
Chen, Xiaole
Kim, Sangbumn
Manning, David R.
Riobo, Natalia A.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Sonic HEDGEHOG
migration
cancer
signal pathways
topic Sonic HEDGEHOG
migration
cancer
signal pathways
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Evidence supporting the functionality of Smoothened (SMO), an essential transducer in most pathways engaged by Hedgehog (Hh), as a Gi-coupled receptor contrasts with the lack of an apparently consistent requirement for Gi in Hh signal transduction. In the present study, we sought to evaluate the role of SMO-Gi coupling in fibroblast migration induced by Sonic Hedgehog (Shh). Our results demonstrate an absolute requirement for Gi in Shh-induced fibroblast migration. We found that Shh acutely stimulates the small Rho GTPases Rac1 and RhoA via SMO through a Gi protein- and PI3K-dependent mechanism, and that these are required for cell migration. These responses were independent of transcription by Gli and of the C-terminal domain of SMO, as we show using a combination of molecular and genetic tools. Our findings provide a mechanistic model for fibroblast migration in response to Shh and underscore the role of SMO-Gi coupling in non-canonical Hh signaling.
Fil: Polizio, Ariel Héctor. Thomas Jefferson University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Chinchilla, Pilar. Thomas Jefferson University; Estados Unidos
Fil: Chen, Xiaole. Thomas Jefferson University; Estados Unidos
Fil: Kim, Sangbumn. Thomas Jefferson University; Estados Unidos
Fil: Manning, David R.. University Of Pennsylvania; Estados Unidos
Fil: Riobo, Natalia A.. Thomas Jefferson University; Estados Unidos
description Evidence supporting the functionality of Smoothened (SMO), an essential transducer in most pathways engaged by Hedgehog (Hh), as a Gi-coupled receptor contrasts with the lack of an apparently consistent requirement for Gi in Hh signal transduction. In the present study, we sought to evaluate the role of SMO-Gi coupling in fibroblast migration induced by Sonic Hedgehog (Shh). Our results demonstrate an absolute requirement for Gi in Shh-induced fibroblast migration. We found that Shh acutely stimulates the small Rho GTPases Rac1 and RhoA via SMO through a Gi protein- and PI3K-dependent mechanism, and that these are required for cell migration. These responses were independent of transcription by Gli and of the C-terminal domain of SMO, as we show using a combination of molecular and genetic tools. Our findings provide a mechanistic model for fibroblast migration in response to Shh and underscore the role of SMO-Gi coupling in non-canonical Hh signaling.
publishDate 2011
dc.date.none.fl_str_mv 2011-07
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/11336/13181
Polizio, Ariel Héctor; Chinchilla, Pilar; Chen, Xiaole; Kim, Sangbumn; Manning, David R.; et al.; Heterotrimeric Gi Proteins link Hedgehog signaling to activation of Rho small GTPases to promote fibroblast migration; American Society For Biochemistry And Molecular Biology; Journal Of Biological Chemistry; 286; 7-2011; 19589-19596
0021-9258
url http://hdl.handle.net/11336/13181
identifier_str_mv Polizio, Ariel Héctor; Chinchilla, Pilar; Chen, Xiaole; Kim, Sangbumn; Manning, David R.; et al.; Heterotrimeric Gi Proteins link Hedgehog signaling to activation of Rho small GTPases to promote fibroblast migration; American Society For Biochemistry And Molecular Biology; Journal Of Biological Chemistry; 286; 7-2011; 19589-19596
0021-9258
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/286/22/19589.long
info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M110.197111
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3103338/
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 American Society For Biochemistry And Molecular Biology
publisher.none.fl_str_mv American Society For Biochemistry And Molecular 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 13.13397

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