Phosphorylation of transcription factor p62TCF by MAP kinase stimulates ternary complex formation at c-fos promoter.
Transcription of the proto-oncogene c-fos is stimulated rapidly and transiently by serum growth factors and mitogens. Critical for this response is the serum-response element which is bound in vivo in a ternary complex containing the transcription factors p67SRF and p62TCF (ref. 2). Disruption of the ternary complex correlates with impaired induction by serum and phorbol ester. Mitogen-activated protein (MAP) kinase is a serine/threonine kinase which is activated 1-5 minutes after treatment of cells with mitogens and growth factors that induce re-entry into the cell cycle, making MAP kinase a candidate for the transmission of proliferative signals. Here we show that p62TCF is phosphorylated by MAP kinase in vitro and that phosphorylation results in enhanced ternary complex formation. Serum-starved Swiss 3T3 cells treated with epidermal growth factor, which induces MAP kinase in these cells, are induced to express c-fos and yield p62TCF active in ternary complex formation. In contrast, treatment of Swiss 3T3 cells with insulin, which does not activate MAP kinase under these conditions, does not lead to enhanced ternary complex formation nor does it induce c-fos transcription. Our results link the expression of the human c-fos proto-oncogene to signal transduction pathways known to be activated before its own induction.
Gille
H
H
Max-Planck-Institut für Immunbiologie, Spemann Laboratories, Freiburg, Germany.
Sharrocks
A D
AD
Shaw
P E
PE
D016475:3T3 Cells; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002455:Cell Division; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D046911:Macromolecular Substances; D051379:Mice; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D007328:Insulin; C000715470:MAS1 protein, human; D046911:Macromolecular Substances; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors; C072545:p62TCF protein, human; C489525:p62TCF protein, mouse; D004815:Epidermal Growth Factor; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases