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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....
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2001
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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 |
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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 |
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