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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/182613
Ver los metadatos del registro completo
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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 |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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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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13.22299 |