Cargando…

Lipid raft microdomain compartmentalization of TC10 is required for insulin signaling and GLUT4 translocation

Recent studies indicate that insulin stimulation of glucose transporter (GLUT)4 translocation requires at least two distinct insulin receptor–mediated signals: one leading to the activation of phosphatidylinositol 3 (PI-3) kinase and the other to the activation of the small GTP binding protein TC10....

Descripción completa

Detalles Bibliográficos
Autores principales: Watson, Robert T., Shigematsu, Satoshi, Chiang, Shian-Huey, Mora, Silvia, Kanzaki, Makoto, Macara, Ian G., Saltiel, Alan R., Pessin, Jeffrey E.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196453/
https://www.ncbi.nlm.nih.gov/pubmed/11502760
http://dx.doi.org/10.1083/jcb.200102078
_version_ 1782148064026296320
author Watson, Robert T.
Shigematsu, Satoshi
Chiang, Shian-Huey
Mora, Silvia
Kanzaki, Makoto
Macara, Ian G.
Saltiel, Alan R.
Pessin, Jeffrey E.
author_facet Watson, Robert T.
Shigematsu, Satoshi
Chiang, Shian-Huey
Mora, Silvia
Kanzaki, Makoto
Macara, Ian G.
Saltiel, Alan R.
Pessin, Jeffrey E.
author_sort Watson, Robert T.
collection PubMed
description Recent studies indicate that insulin stimulation of glucose transporter (GLUT)4 translocation requires at least two distinct insulin receptor–mediated signals: one leading to the activation of phosphatidylinositol 3 (PI-3) kinase and the other to the activation of the small GTP binding protein TC10. We now demonstrate that TC10 is processed through the secretory membrane trafficking system and localizes to caveolin-enriched lipid raft microdomains. Although insulin activated the wild-type TC10 protein and a TC10/H-Ras chimera that were targeted to lipid raft microdomains, it was unable to activate a TC10/K-Ras chimera that was directed to the nonlipid raft domains. Similarly, only the lipid raft–localized TC10/ H-Ras chimera inhibited GLUT4 translocation, whereas the TC10/K-Ras chimera showed no significant inhibitory activity. Furthermore, disruption of lipid raft microdomains by expression of a dominant-interfering caveolin 3 mutant (Cav3/DGV) inhibited the insulin stimulation of GLUT4 translocation and TC10 lipid raft localization and activation without affecting PI-3 kinase signaling. These data demonstrate that the insulin stimulation of GLUT4 translocation in adipocytes requires the spatial separation and distinct compartmentalization of the PI-3 kinase and TC10 signaling pathways.
format Text
id pubmed-2196453
institution National Center for Biotechnology Information
language English
publishDate 2001
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-21964532008-05-01 Lipid raft microdomain compartmentalization of TC10 is required for insulin signaling and GLUT4 translocation Watson, Robert T. Shigematsu, Satoshi Chiang, Shian-Huey Mora, Silvia Kanzaki, Makoto Macara, Ian G. Saltiel, Alan R. Pessin, Jeffrey E. J Cell Biol Research Article Recent studies indicate that insulin stimulation of glucose transporter (GLUT)4 translocation requires at least two distinct insulin receptor–mediated signals: one leading to the activation of phosphatidylinositol 3 (PI-3) kinase and the other to the activation of the small GTP binding protein TC10. We now demonstrate that TC10 is processed through the secretory membrane trafficking system and localizes to caveolin-enriched lipid raft microdomains. Although insulin activated the wild-type TC10 protein and a TC10/H-Ras chimera that were targeted to lipid raft microdomains, it was unable to activate a TC10/K-Ras chimera that was directed to the nonlipid raft domains. Similarly, only the lipid raft–localized TC10/ H-Ras chimera inhibited GLUT4 translocation, whereas the TC10/K-Ras chimera showed no significant inhibitory activity. Furthermore, disruption of lipid raft microdomains by expression of a dominant-interfering caveolin 3 mutant (Cav3/DGV) inhibited the insulin stimulation of GLUT4 translocation and TC10 lipid raft localization and activation without affecting PI-3 kinase signaling. These data demonstrate that the insulin stimulation of GLUT4 translocation in adipocytes requires the spatial separation and distinct compartmentalization of the PI-3 kinase and TC10 signaling pathways. The Rockefeller University Press 2001-08-20 /pmc/articles/PMC2196453/ /pubmed/11502760 http://dx.doi.org/10.1083/jcb.200102078 Text en Copyright © 2001, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Article
Watson, Robert T.
Shigematsu, Satoshi
Chiang, Shian-Huey
Mora, Silvia
Kanzaki, Makoto
Macara, Ian G.
Saltiel, Alan R.
Pessin, Jeffrey E.
Lipid raft microdomain compartmentalization of TC10 is required for insulin signaling and GLUT4 translocation
title Lipid raft microdomain compartmentalization of TC10 is required for insulin signaling and GLUT4 translocation
title_full Lipid raft microdomain compartmentalization of TC10 is required for insulin signaling and GLUT4 translocation
title_fullStr Lipid raft microdomain compartmentalization of TC10 is required for insulin signaling and GLUT4 translocation
title_full_unstemmed Lipid raft microdomain compartmentalization of TC10 is required for insulin signaling and GLUT4 translocation
title_short Lipid raft microdomain compartmentalization of TC10 is required for insulin signaling and GLUT4 translocation
title_sort lipid raft microdomain compartmentalization of tc10 is required for insulin signaling and glut4 translocation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196453/
https://www.ncbi.nlm.nih.gov/pubmed/11502760
http://dx.doi.org/10.1083/jcb.200102078
work_keys_str_mv AT watsonrobertt lipidraftmicrodomaincompartmentalizationoftc10isrequiredforinsulinsignalingandglut4translocation
AT shigematsusatoshi lipidraftmicrodomaincompartmentalizationoftc10isrequiredforinsulinsignalingandglut4translocation
AT chiangshianhuey lipidraftmicrodomaincompartmentalizationoftc10isrequiredforinsulinsignalingandglut4translocation
AT morasilvia lipidraftmicrodomaincompartmentalizationoftc10isrequiredforinsulinsignalingandglut4translocation
AT kanzakimakoto lipidraftmicrodomaincompartmentalizationoftc10isrequiredforinsulinsignalingandglut4translocation
AT macaraiang lipidraftmicrodomaincompartmentalizationoftc10isrequiredforinsulinsignalingandglut4translocation
AT saltielalanr lipidraftmicrodomaincompartmentalizationoftc10isrequiredforinsulinsignalingandglut4translocation
AT pessinjeffreye lipidraftmicrodomaincompartmentalizationoftc10isrequiredforinsulinsignalingandglut4translocation