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.
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16 April 2001
Article|
April 09 2001
Integrin-Mediated Adhesion Regulates ERK Nuclear Translocation and Phosphorylation of Elk-1
Andrew E. Aplin,
Andrew E. Aplin
aDepartment of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
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Sheryl A. Stewart,
Sheryl A. Stewart
bDepartment of Pharmacology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19087
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Richard K. Assoian,
Richard K. Assoian
bDepartment of Pharmacology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19087
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R.L. Juliano
R.L. Juliano
aDepartment of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
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Andrew E. Aplin
aDepartment of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
Sheryl A. Stewart
bDepartment of Pharmacology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19087
Richard K. Assoian
bDepartment of Pharmacology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19087
R.L. Juliano
aDepartment of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
Abbreviations used in this paper: CCD, cytochalasin D; ERK, extracellular signal–regulated kinase; FAK, focal adhesion kinase; HA, hemagglutinin; MAP, mitogen-activated protein; MEK, MAP kinase/ERK kinase; MKP, MAP kinase phosphatase.
Received:
November 03 2000
Revision Requested:
January 16 2001
Accepted:
February 20 2001
Online ISSN: 1540-8140
Print ISSN: 0021-9525
© 2001 The Rockefeller University Press
2001
The Rockefeller University Press
J Cell Biol (2001) 153 (2): 273–282.
Article history
Received:
November 03 2000
Revision Requested:
January 16 2001
Accepted:
February 20 2001
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Citation
Andrew E. Aplin, Sheryl A. Stewart, Richard K. Assoian, R.L. Juliano; Integrin-Mediated Adhesion Regulates ERK Nuclear Translocation and Phosphorylation of Elk-1. J Cell Biol 16 April 2001; 153 (2): 273–282. doi: https://doi.org/10.1083/jcb.153.2.273
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