Insulin-stimulated expression of c-fos, fra1 and c-jun accompanies the activation of the activator protein-1 (AP-1) transcriptional complex.
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.
Griffiths
M R
MR
Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.
Black
E J
EJ
Culbert
A A
AA
Dickens
M
M
Shaw
P E
PE
Gillespie
D A
DA
Tavaré
J M
JM
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D007328:Insulin / Q000494:pharmacology*; D046911:Macromolecular Substances; D011401:Promoter Regions, Genetic / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis*; D018808:Transcription Factor AP-1 / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D000099169:Fos-Related Antigen 1
D004247:DNA; D007328:Insulin; D046911:Macromolecular Substances; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D000099169:Fos-Related Antigen 1