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Integrin-Mediated Adhesion Regulates ERK Nuclear Translocation and Phosphorylation of Elk-1
Integrin-mediated adhesion to the extracellular matrix permits efficient growth factor-mediated activation of extracellular signal–regulated kinases (ERKs). Points of regulation have been localized to the level of receptor phosphorylation or to activation of the downstream components, Raf and MEK (m...
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/PMC2169466/ https://www.ncbi.nlm.nih.gov/pubmed/11309409 |
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author | Aplin, Andrew E. Stewart, Sheryl A. Assoian, Richard K. Juliano, R.L. |
author_facet | Aplin, Andrew E. Stewart, Sheryl A. Assoian, Richard K. Juliano, R.L. |
author_sort | Aplin, Andrew E. |
collection | PubMed |
description | Integrin-mediated adhesion to the extracellular matrix permits efficient growth factor-mediated activation of extracellular signal–regulated kinases (ERKs). Points of regulation have been localized to the level of receptor phosphorylation or to activation of the downstream components, Raf and MEK (mitogen-activated protein kinase/ERK kinase). However, it is also well established that ERK translocation from the cytoplasm to the nucleus is required for G1 phase cell cycle progression. Here we show that phosphorylation of the nuclear ERK substrate, Elk-1 at serine 383, is anchorage dependent in response to growth factor treatment of NIH 3T3 fibroblasts. Furthermore, when we activated ERK in nonadherent cells by expression of active components of the ERK cascade, subsequent phosphorylation of Elk-1 at serine 383 and Elk-1–mediated transactivation were still impaired compared with adherent cells. Elk-1 phosphorylation was dependent on an intact actin cytoskeleton, as discerned by treatment with cytochalasin D (CCD). Finally, expression of active MEK failed to predominantly localize ERK to the nucleus in suspended cells or adherent cells treated with CCD. These data show that integrin-mediated organization of the actin cytoskeleton regulates localization of activated ERK, and in turn the ability of ERK to efficiently phosphorylate nuclear substrates. |
format | Text |
id | pubmed-2169466 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2001 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21694662008-05-01 Integrin-Mediated Adhesion Regulates ERK Nuclear Translocation and Phosphorylation of Elk-1 Aplin, Andrew E. Stewart, Sheryl A. Assoian, Richard K. Juliano, R.L. J Cell Biol Original Article Integrin-mediated adhesion to the extracellular matrix permits efficient growth factor-mediated activation of extracellular signal–regulated kinases (ERKs). Points of regulation have been localized to the level of receptor phosphorylation or to activation of the downstream components, Raf and MEK (mitogen-activated protein kinase/ERK kinase). However, it is also well established that ERK translocation from the cytoplasm to the nucleus is required for G1 phase cell cycle progression. Here we show that phosphorylation of the nuclear ERK substrate, Elk-1 at serine 383, is anchorage dependent in response to growth factor treatment of NIH 3T3 fibroblasts. Furthermore, when we activated ERK in nonadherent cells by expression of active components of the ERK cascade, subsequent phosphorylation of Elk-1 at serine 383 and Elk-1–mediated transactivation were still impaired compared with adherent cells. Elk-1 phosphorylation was dependent on an intact actin cytoskeleton, as discerned by treatment with cytochalasin D (CCD). Finally, expression of active MEK failed to predominantly localize ERK to the nucleus in suspended cells or adherent cells treated with CCD. These data show that integrin-mediated organization of the actin cytoskeleton regulates localization of activated ERK, and in turn the ability of ERK to efficiently phosphorylate nuclear substrates. The Rockefeller University Press 2001-04-16 /pmc/articles/PMC2169466/ /pubmed/11309409 Text en © 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 | Original Article Aplin, Andrew E. Stewart, Sheryl A. Assoian, Richard K. Juliano, R.L. Integrin-Mediated Adhesion Regulates ERK Nuclear Translocation and Phosphorylation of Elk-1 |
title | Integrin-Mediated Adhesion Regulates ERK Nuclear Translocation and Phosphorylation of Elk-1 |
title_full | Integrin-Mediated Adhesion Regulates ERK Nuclear Translocation and Phosphorylation of Elk-1 |
title_fullStr | Integrin-Mediated Adhesion Regulates ERK Nuclear Translocation and Phosphorylation of Elk-1 |
title_full_unstemmed | Integrin-Mediated Adhesion Regulates ERK Nuclear Translocation and Phosphorylation of Elk-1 |
title_short | Integrin-Mediated Adhesion Regulates ERK Nuclear Translocation and Phosphorylation of Elk-1 |
title_sort | integrin-mediated adhesion regulates erk nuclear translocation and phosphorylation of elk-1 |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2169466/ https://www.ncbi.nlm.nih.gov/pubmed/11309409 |
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