Giα proteins exhibit functional differences in the activation of ERK1/2, Akt and mTORC1 by growth factors in normal and breast cancer cells

Autores
Wang, Zhanwei; Dela Cruz, Rica; Ji, Fang; Guo, Sheng; Zhang, Jianhua; Wang, Ying; Feng, Gen-Sheng; Birnbaumer, Lutz; Jiang, Meisheng; Chu, Wen Ming
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background In a classic model, Giα proteins including Gi1α, Gi2α and Gi3α are important for transducing signals from Giα protein-coupled receptors (GiαPCRs) to their downstream cascades in response to hormones and neurotransmitters. Our previous study has suggested that Gi1α, Gi2α and Gi3α are also important for the activation of the PI3K/Akt/mTORC1 pathway by epidermal growth factor (EGF) and its family members. However, a genetic role of these Giα proteins in the activation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) by EGF is largely unknown. Further, it is not clear whether these Giα proteins are also engaged in the activation of both the Akt/mTORC1 and ERK1/2 pathways by other growth factor family members. Additionally, a role of these Giα proteins in breast cancer remains to be elucidated. Results We found that Gi1/3 deficient MEFs with the low expression level of Gi2α showed defective ERK1/2 activation by EGFs, IGF-1 and insulin, and Akt and mTORC1 activation by EGFs and FGFs. Gi1/2/3 knockdown breast cancer cells exhibited a similar defect in the activations and a defect in in vitro growth and invasion. The Giα proteins associated with RTKs, Gab1, FRS2 and Shp2 in breast cancer cells and their ablation impaired Gab1’s interactions with Shp2 in response to EGF and IGF-1, or with FRS2 and Grb2 in response to bFGF. Conclusions Giα proteins differentially regulate the activation of Akt, mTORC1 and ERK1/2 by different families of growth factors. Giα proteins are important for breast cancer cell growth and invasion.
Fil: Wang, Zhanwei. University of Hawaii Cancer Center. Honolulu; Estados Unidos
Fil: Dela Cruz, Rica. University of Hawaii Cancer Center. Honolulu; Estados Unidos
Fil: Ji, Fang. Shanghai Jiao Tong University . Sahnghai; China
Fil: Guo, Sheng. University of Hawaii Cancer Center. Honolulu; Estados Unidos. Shanghai Jiaotong University. Shangha; Estados Unidos
Fil: Zhang, Jianhua. Shanghai Jiaotong University. Shangha; Estados Unidos. University of Hawaii Cancer Center. Honolulu; Estados Unidos
Fil: Wang, Ying. David Geffen School of Medicine at UCLA. Los Angeles; Estados Unidos
Fil: Feng, Gen-Sheng. University of California at San Diego; Estados Unidos
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institutes of Health; Estados Unidos
Fil: Jiang, Meisheng. David Geffen School of Medicine at UCLA. Los Angeles; Estados Unidos
Fil: Chu, Wen Ming. University of Hawaii Cancer Center. Honolulu; Estados Unidos
Materia
Giα proteins
receptor tyrosine kinase (RTK)
EGFR
Gab1
Shp2
EGF
Akt
mTORC1
ERK1/2
breastcancer
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:11336/33216
Acceder
id CONICETDig_766d9d29f555598fb641016a02b259e7
oai_identifier_str oai:ri.conicet.gov.ar:11336/33216
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Giα proteins exhibit functional differences in the activation of ERK1/2, Akt and mTORC1 by growth factors in normal and breast cancer cellsWang, ZhanweiDela Cruz, RicaJi, FangGuo, ShengZhang, JianhuaWang, YingFeng, Gen-ShengBirnbaumer, LutzJiang, MeishengChu, Wen MingGiα proteinsreceptor tyrosine kinase (RTK)EGFRGab1Shp2EGFAktmTORC1ERK1/2breastcancerhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Background In a classic model, Giα proteins including Gi1α, Gi2α and Gi3α are important for transducing signals from Giα protein-coupled receptors (GiαPCRs) to their downstream cascades in response to hormones and neurotransmitters. Our previous study has suggested that Gi1α, Gi2α and Gi3α are also important for the activation of the PI3K/Akt/mTORC1 pathway by epidermal growth factor (EGF) and its family members. However, a genetic role of these Giα proteins in the activation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) by EGF is largely unknown. Further, it is not clear whether these Giα proteins are also engaged in the activation of both the Akt/mTORC1 and ERK1/2 pathways by other growth factor family members. Additionally, a role of these Giα proteins in breast cancer remains to be elucidated. Results We found that Gi1/3 deficient MEFs with the low expression level of Gi2α showed defective ERK1/2 activation by EGFs, IGF-1 and insulin, and Akt and mTORC1 activation by EGFs and FGFs. Gi1/2/3 knockdown breast cancer cells exhibited a similar defect in the activations and a defect in in vitro growth and invasion. The Giα proteins associated with RTKs, Gab1, FRS2 and Shp2 in breast cancer cells and their ablation impaired Gab1’s interactions with Shp2 in response to EGF and IGF-1, or with FRS2 and Grb2 in response to bFGF. Conclusions Giα proteins differentially regulate the activation of Akt, mTORC1 and ERK1/2 by different families of growth factors. Giα proteins are important for breast cancer cell growth and invasion.Fil: Wang, Zhanwei. University of Hawaii Cancer Center. Honolulu; Estados UnidosFil: Dela Cruz, Rica. University of Hawaii Cancer Center. Honolulu; Estados UnidosFil: Ji, Fang. Shanghai Jiao Tong University . Sahnghai; ChinaFil: Guo, Sheng. University of Hawaii Cancer Center. Honolulu; Estados Unidos. Shanghai Jiaotong University. Shangha; Estados UnidosFil: Zhang, Jianhua. Shanghai Jiaotong University. Shangha; Estados Unidos. University of Hawaii Cancer Center. Honolulu; Estados UnidosFil: Wang, Ying. David Geffen School of Medicine at UCLA. Los Angeles; Estados UnidosFil: Feng, Gen-Sheng. University of California at San Diego; Estados UnidosFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institutes of Health; Estados UnidosFil: Jiang, Meisheng. David Geffen School of Medicine at UCLA. Los Angeles; Estados UnidosFil: Chu, Wen Ming. University of Hawaii Cancer Center. Honolulu; Estados UnidosBioMed Central2014-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/33216Guo, Sheng; Birnbaumer, Lutz; Zhang, Jianhua; Wang, Ying; Ji, Fang; Dela Cruz, Rica; et al.; Giα proteins exhibit functional differences in the activation of ERK1/2, Akt and mTORC1 by growth factors in normal and breast cancer cells; BioMed Central; Cell Communication and Signaling; 2014; 2-2014; 1-121478-811XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1186/1478-811X-12-10info:eu-repo/semantics/altIdentifier/url/https://biosignaling.biomedcentral.com/articles/10.1186/1478-811X-12-10info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T11:30:35Zoai:ri.conicet.gov.ar:11336/33216instacron: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:34982025-09-17 11:30:35.36CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Giα proteins exhibit functional differences in the activation of ERK1/2, Akt and mTORC1 by growth factors in normal and breast cancer cells
title Giα proteins exhibit functional differences in the activation of ERK1/2, Akt and mTORC1 by growth factors in normal and breast cancer cells
spellingShingle Giα proteins exhibit functional differences in the activation of ERK1/2, Akt and mTORC1 by growth factors in normal and breast cancer cells
Wang, Zhanwei
Giα proteins
receptor tyrosine kinase (RTK)
EGFR
Gab1
Shp2
EGF
Akt
mTORC1
ERK1/2
breastcancer
title_short Giα proteins exhibit functional differences in the activation of ERK1/2, Akt and mTORC1 by growth factors in normal and breast cancer cells
title_full Giα proteins exhibit functional differences in the activation of ERK1/2, Akt and mTORC1 by growth factors in normal and breast cancer cells
title_fullStr Giα proteins exhibit functional differences in the activation of ERK1/2, Akt and mTORC1 by growth factors in normal and breast cancer cells
title_full_unstemmed Giα proteins exhibit functional differences in the activation of ERK1/2, Akt and mTORC1 by growth factors in normal and breast cancer cells
title_sort Giα proteins exhibit functional differences in the activation of ERK1/2, Akt and mTORC1 by growth factors in normal and breast cancer cells
dc.creator.none.fl_str_mv Wang, Zhanwei
Dela Cruz, Rica
Ji, Fang
Guo, Sheng
Zhang, Jianhua
Wang, Ying
Feng, Gen-Sheng
Birnbaumer, Lutz
Jiang, Meisheng
Chu, Wen Ming
author Wang, Zhanwei
author_facet Wang, Zhanwei
Dela Cruz, Rica
Ji, Fang
Guo, Sheng
Zhang, Jianhua
Wang, Ying
Feng, Gen-Sheng
Birnbaumer, Lutz
Jiang, Meisheng
Chu, Wen Ming
author_role author
author2 Dela Cruz, Rica
Ji, Fang
Guo, Sheng
Zhang, Jianhua
Wang, Ying
Feng, Gen-Sheng
Birnbaumer, Lutz
Jiang, Meisheng
Chu, Wen Ming
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Giα proteins
receptor tyrosine kinase (RTK)
EGFR
Gab1
Shp2
EGF
Akt
mTORC1
ERK1/2
breastcancer
topic Giα proteins
receptor tyrosine kinase (RTK)
EGFR
Gab1
Shp2
EGF
Akt
mTORC1
ERK1/2
breastcancer
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Background In a classic model, Giα proteins including Gi1α, Gi2α and Gi3α are important for transducing signals from Giα protein-coupled receptors (GiαPCRs) to their downstream cascades in response to hormones and neurotransmitters. Our previous study has suggested that Gi1α, Gi2α and Gi3α are also important for the activation of the PI3K/Akt/mTORC1 pathway by epidermal growth factor (EGF) and its family members. However, a genetic role of these Giα proteins in the activation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) by EGF is largely unknown. Further, it is not clear whether these Giα proteins are also engaged in the activation of both the Akt/mTORC1 and ERK1/2 pathways by other growth factor family members. Additionally, a role of these Giα proteins in breast cancer remains to be elucidated. Results We found that Gi1/3 deficient MEFs with the low expression level of Gi2α showed defective ERK1/2 activation by EGFs, IGF-1 and insulin, and Akt and mTORC1 activation by EGFs and FGFs. Gi1/2/3 knockdown breast cancer cells exhibited a similar defect in the activations and a defect in in vitro growth and invasion. The Giα proteins associated with RTKs, Gab1, FRS2 and Shp2 in breast cancer cells and their ablation impaired Gab1’s interactions with Shp2 in response to EGF and IGF-1, or with FRS2 and Grb2 in response to bFGF. Conclusions Giα proteins differentially regulate the activation of Akt, mTORC1 and ERK1/2 by different families of growth factors. Giα proteins are important for breast cancer cell growth and invasion.
Fil: Wang, Zhanwei. University of Hawaii Cancer Center. Honolulu; Estados Unidos
Fil: Dela Cruz, Rica. University of Hawaii Cancer Center. Honolulu; Estados Unidos
Fil: Ji, Fang. Shanghai Jiao Tong University . Sahnghai; China
Fil: Guo, Sheng. University of Hawaii Cancer Center. Honolulu; Estados Unidos. Shanghai Jiaotong University. Shangha; Estados Unidos
Fil: Zhang, Jianhua. Shanghai Jiaotong University. Shangha; Estados Unidos. University of Hawaii Cancer Center. Honolulu; Estados Unidos
Fil: Wang, Ying. David Geffen School of Medicine at UCLA. Los Angeles; Estados Unidos
Fil: Feng, Gen-Sheng. University of California at San Diego; Estados Unidos
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institutes of Health; Estados Unidos
Fil: Jiang, Meisheng. David Geffen School of Medicine at UCLA. Los Angeles; Estados Unidos
Fil: Chu, Wen Ming. University of Hawaii Cancer Center. Honolulu; Estados Unidos
description Background In a classic model, Giα proteins including Gi1α, Gi2α and Gi3α are important for transducing signals from Giα protein-coupled receptors (GiαPCRs) to their downstream cascades in response to hormones and neurotransmitters. Our previous study has suggested that Gi1α, Gi2α and Gi3α are also important for the activation of the PI3K/Akt/mTORC1 pathway by epidermal growth factor (EGF) and its family members. However, a genetic role of these Giα proteins in the activation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) by EGF is largely unknown. Further, it is not clear whether these Giα proteins are also engaged in the activation of both the Akt/mTORC1 and ERK1/2 pathways by other growth factor family members. Additionally, a role of these Giα proteins in breast cancer remains to be elucidated. Results We found that Gi1/3 deficient MEFs with the low expression level of Gi2α showed defective ERK1/2 activation by EGFs, IGF-1 and insulin, and Akt and mTORC1 activation by EGFs and FGFs. Gi1/2/3 knockdown breast cancer cells exhibited a similar defect in the activations and a defect in in vitro growth and invasion. The Giα proteins associated with RTKs, Gab1, FRS2 and Shp2 in breast cancer cells and their ablation impaired Gab1’s interactions with Shp2 in response to EGF and IGF-1, or with FRS2 and Grb2 in response to bFGF. Conclusions Giα proteins differentially regulate the activation of Akt, mTORC1 and ERK1/2 by different families of growth factors. Giα proteins are important for breast cancer cell growth and invasion.
publishDate 2014
dc.date.none.fl_str_mv 2014-02
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/11336/33216
Guo, Sheng; Birnbaumer, Lutz; Zhang, Jianhua; Wang, Ying; Ji, Fang; Dela Cruz, Rica; et al.; Giα proteins exhibit functional differences in the activation of ERK1/2, Akt and mTORC1 by growth factors in normal and breast cancer cells; BioMed Central; Cell Communication and Signaling; 2014; 2-2014; 1-12
1478-811X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/33216
identifier_str_mv Guo, Sheng; Birnbaumer, Lutz; Zhang, Jianhua; Wang, Ying; Ji, Fang; Dela Cruz, Rica; et al.; Giα proteins exhibit functional differences in the activation of ERK1/2, Akt and mTORC1 by growth factors in normal and breast cancer cells; BioMed Central; Cell Communication and Signaling; 2014; 2-2014; 1-12
1478-811X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1186/1478-811X-12-10
info:eu-repo/semantics/altIdentifier/url/https://biosignaling.biomedcentral.com/articles/10.1186/1478-811X-12-10
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 BioMed Central
publisher.none.fl_str_mv BioMed Central
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 13.001348

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