Proteome and phosphoproteome analysis of brown adipocytes reveals that RICTOR loss dampens global insulin/AKT signaling

Autores
Entwisle, Samuel W.; Martinez Calejman, Camila; Valente, Anthony S.; Lawrence, Robert T.; Hung, Chien Min; Guertin, David A.; Villen, Judit
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Stimulating brown adipose tissue (BAT) activity represents a promising therapy for overcoming metabolic diseases. mTORC2 is important for regulating BAT metabolism, but its downstream targets have not been fully characterized. In this study, we apply proteomics and phosphoproteomics to investigate the downstream effectors of mTORC2 in brown adipocytes. We compare wild-type controls to isogenic cells with an induced knockout of the mTORC2 subunit RICTOR (Rictor-iKO) by stimulating each with insulin for a 30-minute time course. In Rictor-iKO cells, we identify decreases to the abundance of glycolytic and de novo lipogenesis enzymes, and increases to mitochondrial proteins as well as a set of proteins known to increase upon interferon stimulation. We also observe significant differences to basal phosphorylation due to chronic RICTOR loss including decreased phosphorylation of the lipid droplet protein perilipin-1 in Rictor-iKO cells, suggesting that RICTOR could be involved with regulating basal lipolysis or droplet dynamics. Finally, we observe mild dampening of acute insulin signaling response in Rictor-iKO cells, and a subset of AKT substrates exhibiting statistically significant dependence on RICTOR.
Fil: Entwisle, Samuel W.. University of Washington; Estados Unidos
Fil: Martinez Calejman, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Valente, Anthony S.. University of Washington; Estados Unidos
Fil: Lawrence, Robert T.. University of Washington; Estados Unidos
Fil: Hung, Chien Min. University Of Massachussets. Medical School; Estados Unidos
Fil: Guertin, David A.. University Of Massachussets. Medical School; Estados Unidos
Fil: Villen, Judit. University of Washington; Estados Unidos
Materia
mTORC2
Brown adipocytes
AKT
insulin
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:11336/182613
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/182613
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Proteome and phosphoproteome analysis of brown adipocytes reveals that RICTOR loss dampens global insulin/AKT signalingEntwisle, Samuel W.Martinez Calejman, CamilaValente, Anthony S.Lawrence, Robert T.Hung, Chien MinGuertin, David A.Villen, JuditmTORC2Brown adipocytesAKTinsulinhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Stimulating brown adipose tissue (BAT) activity represents a promising therapy for overcoming metabolic diseases. mTORC2 is important for regulating BAT metabolism, but its downstream targets have not been fully characterized. In this study, we apply proteomics and phosphoproteomics to investigate the downstream effectors of mTORC2 in brown adipocytes. We compare wild-type controls to isogenic cells with an induced knockout of the mTORC2 subunit RICTOR (Rictor-iKO) by stimulating each with insulin for a 30-minute time course. In Rictor-iKO cells, we identify decreases to the abundance of glycolytic and de novo lipogenesis enzymes, and increases to mitochondrial proteins as well as a set of proteins known to increase upon interferon stimulation. We also observe significant differences to basal phosphorylation due to chronic RICTOR loss including decreased phosphorylation of the lipid droplet protein perilipin-1 in Rictor-iKO cells, suggesting that RICTOR could be involved with regulating basal lipolysis or droplet dynamics. Finally, we observe mild dampening of acute insulin signaling response in Rictor-iKO cells, and a subset of AKT substrates exhibiting statistically significant dependence on RICTOR.Fil: Entwisle, Samuel W.. University of Washington; Estados UnidosFil: Martinez Calejman, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Valente, Anthony S.. University of Washington; Estados UnidosFil: Lawrence, Robert T.. University of Washington; Estados UnidosFil: Hung, Chien Min. University Of Massachussets. Medical School; Estados UnidosFil: Guertin, David A.. University Of Massachussets. Medical School; Estados UnidosFil: Villen, Judit. University of Washington; Estados UnidosAmerican Society for Biochemistry and Molecular Biology2020-07info: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/11336/182613Entwisle, Samuel W.; Martinez Calejman, Camila; Valente, Anthony S.; Lawrence, Robert T.; Hung, Chien Min; et al.; Proteome and phosphoproteome analysis of brown adipocytes reveals that RICTOR loss dampens global insulin/AKT signaling; American Society for Biochemistry and Molecular Biology; Molecular & Cellular Proteomics; 19; 7; 7-2020; 1104-11191535-9476CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.mcponline.org/lookup/doi/10.1074/mcp.RA120.001946info:eu-repo/semantics/altIdentifier/doi/10.1074/mcp.RA120.001946info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:27:26Zoai:ri.conicet.gov.ar:11336/182613instacron: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:34982025-10-15 15:27:27.151CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Proteome and phosphoproteome analysis of brown adipocytes reveals that RICTOR loss dampens global insulin/AKT signaling
title Proteome and phosphoproteome analysis of brown adipocytes reveals that RICTOR loss dampens global insulin/AKT signaling
spellingShingle Proteome and phosphoproteome analysis of brown adipocytes reveals that RICTOR loss dampens global insulin/AKT signaling
Entwisle, Samuel W.
mTORC2
Brown adipocytes
AKT
insulin
title_short Proteome and phosphoproteome analysis of brown adipocytes reveals that RICTOR loss dampens global insulin/AKT signaling
title_full Proteome and phosphoproteome analysis of brown adipocytes reveals that RICTOR loss dampens global insulin/AKT signaling
title_fullStr Proteome and phosphoproteome analysis of brown adipocytes reveals that RICTOR loss dampens global insulin/AKT signaling
title_full_unstemmed Proteome and phosphoproteome analysis of brown adipocytes reveals that RICTOR loss dampens global insulin/AKT signaling
title_sort Proteome and phosphoproteome analysis of brown adipocytes reveals that RICTOR loss dampens global insulin/AKT signaling
dc.creator.none.fl_str_mv Entwisle, Samuel W.
Martinez Calejman, Camila
Valente, Anthony S.
Lawrence, Robert T.
Hung, Chien Min
Guertin, David A.
Villen, Judit
author Entwisle, Samuel W.
author_facet Entwisle, Samuel W.
Martinez Calejman, Camila
Valente, Anthony S.
Lawrence, Robert T.
Hung, Chien Min
Guertin, David A.
Villen, Judit
author_role author
author2 Martinez Calejman, Camila
Valente, Anthony S.
Lawrence, Robert T.
Hung, Chien Min
Guertin, David A.
Villen, Judit
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv mTORC2
Brown adipocytes
AKT
insulin
topic mTORC2
Brown adipocytes
AKT
insulin
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Stimulating brown adipose tissue (BAT) activity represents a promising therapy for overcoming metabolic diseases. mTORC2 is important for regulating BAT metabolism, but its downstream targets have not been fully characterized. In this study, we apply proteomics and phosphoproteomics to investigate the downstream effectors of mTORC2 in brown adipocytes. We compare wild-type controls to isogenic cells with an induced knockout of the mTORC2 subunit RICTOR (Rictor-iKO) by stimulating each with insulin for a 30-minute time course. In Rictor-iKO cells, we identify decreases to the abundance of glycolytic and de novo lipogenesis enzymes, and increases to mitochondrial proteins as well as a set of proteins known to increase upon interferon stimulation. We also observe significant differences to basal phosphorylation due to chronic RICTOR loss including decreased phosphorylation of the lipid droplet protein perilipin-1 in Rictor-iKO cells, suggesting that RICTOR could be involved with regulating basal lipolysis or droplet dynamics. Finally, we observe mild dampening of acute insulin signaling response in Rictor-iKO cells, and a subset of AKT substrates exhibiting statistically significant dependence on RICTOR.
Fil: Entwisle, Samuel W.. University of Washington; Estados Unidos
Fil: Martinez Calejman, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Valente, Anthony S.. University of Washington; Estados Unidos
Fil: Lawrence, Robert T.. University of Washington; Estados Unidos
Fil: Hung, Chien Min. University Of Massachussets. Medical School; Estados Unidos
Fil: Guertin, David A.. University Of Massachussets. Medical School; Estados Unidos
Fil: Villen, Judit. University of Washington; Estados Unidos
description Stimulating brown adipose tissue (BAT) activity represents a promising therapy for overcoming metabolic diseases. mTORC2 is important for regulating BAT metabolism, but its downstream targets have not been fully characterized. In this study, we apply proteomics and phosphoproteomics to investigate the downstream effectors of mTORC2 in brown adipocytes. We compare wild-type controls to isogenic cells with an induced knockout of the mTORC2 subunit RICTOR (Rictor-iKO) by stimulating each with insulin for a 30-minute time course. In Rictor-iKO cells, we identify decreases to the abundance of glycolytic and de novo lipogenesis enzymes, and increases to mitochondrial proteins as well as a set of proteins known to increase upon interferon stimulation. We also observe significant differences to basal phosphorylation due to chronic RICTOR loss including decreased phosphorylation of the lipid droplet protein perilipin-1 in Rictor-iKO cells, suggesting that RICTOR could be involved with regulating basal lipolysis or droplet dynamics. Finally, we observe mild dampening of acute insulin signaling response in Rictor-iKO cells, and a subset of AKT substrates exhibiting statistically significant dependence on RICTOR.
publishDate 2020
dc.date.none.fl_str_mv 2020-07
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/11336/182613
Entwisle, Samuel W.; Martinez Calejman, Camila; Valente, Anthony S.; Lawrence, Robert T.; Hung, Chien Min; et al.; Proteome and phosphoproteome analysis of brown adipocytes reveals that RICTOR loss dampens global insulin/AKT signaling; American Society for Biochemistry and Molecular Biology; Molecular & Cellular Proteomics; 19; 7; 7-2020; 1104-1119
1535-9476
CONICET Digital
CONICET
url http://hdl.handle.net/11336/182613
identifier_str_mv Entwisle, Samuel W.; Martinez Calejman, Camila; Valente, Anthony S.; Lawrence, Robert T.; Hung, Chien Min; et al.; Proteome and phosphoproteome analysis of brown adipocytes reveals that RICTOR loss dampens global insulin/AKT signaling; American Society for Biochemistry and Molecular Biology; Molecular & Cellular Proteomics; 19; 7; 7-2020; 1104-1119
1535-9476
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.mcponline.org/lookup/doi/10.1074/mcp.RA120.001946
info:eu-repo/semantics/altIdentifier/doi/10.1074/mcp.RA120.001946
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 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
_version_ 1846083416358912000
score 13.22299

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