The activator protein-1 (AP-1) transcriptional complex is made up of members of the Fos (c-Fos, FosB, Fra1, Fra2) and Jun (c-Jun, JunB, JunD) families and is stimulated by insulin in several cell types. The mechanism by which insulin activates this complex is not well understood but it is dependent on the activation of the Erk1 and Erk2 isoforms of mitogen-activated protein kinases. In the current study we show that the AP-1 complex isolated from insulin-stimulated cells contained c-Fos, Fra1, c-Jun and JunB. The activation of the AP-1 complex by insulin was accompanied by (i) a transient increase in c-fos expression, and the transactivation of the ternary complex factors Elk1 and Sap1a, in an Erk1/Erk2-dependent fashion; (ii) a substantial increase in the expression of Fra1 protein and mRNA, which was preceded by a transient decrease in its electrophoretic mobility upon SDS/PAGE, indicative of phosphorylation; and (iii) a sustained increase in c-jun expression without increasing c-Jun phosphorylation on serines 63 and 73 or activation of the stress-activated kinase JNK/SAPK. In conclusion, insulin appears to stimulate the activity of the AP-1 complex primarily through a change in the abundance of the components of this complex, although there may be an additional role for Fra1 phosphorylation.
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October 1998
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Research Article|
October 01 1998
Insulin-stimulated expression of c-fos, fra1 and c-jun accompanies the activation of the activator protein-1 (AP-1) transcriptional complex Available to Purchase
Matthew R. GRIFFITHS;
Matthew R. GRIFFITHS
*Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, U.K.
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Elizabeth J. BLACK;
Elizabeth J. BLACK
†Cancer Research Campaign, Beatson Laboratories, Bearsden, Glasgow G61 1BD, U.K.
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Ainsley A. CULBERT;
Ainsley A. CULBERT
*Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, U.K.
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Martin DICKENS;
Martin DICKENS
*Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, U.K.
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Peter E. SHAW;
Peter E. SHAW
‡Department of Biochemistry, The Medical School, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, U.K.
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David A. F. GILLESPIE;
David A. F. GILLESPIE
†Cancer Research Campaign, Beatson Laboratories, Bearsden, Glasgow G61 1BD, U.K.
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Jeremy M. TAVARÉ
Jeremy M. TAVARÉ
1
*Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, U.K.
1To whom correspondence should be addressed (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
March 26 1998
Revision Received:
July 06 1998
Accepted:
July 27 1998
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1998
1998
Biochem J (1998) 335 (1): 19–26.
Article history
Received:
March 26 1998
Revision Received:
July 06 1998
Accepted:
July 27 1998
Citation
Matthew R. GRIFFITHS, Elizabeth J. BLACK, Ainsley A. CULBERT, Martin DICKENS, Peter E. SHAW, David A. F. GILLESPIE, Jeremy M. TAVARÉ; Insulin-stimulated expression of c-fos, fra1 and c-jun accompanies the activation of the activator protein-1 (AP-1) transcriptional complex. Biochem J 1 October 1998; 335 (1): 19–26. doi: https://doi.org/10.1042/bj3350019
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