Epidermal growth factor induction of the c-jun promoter by a Rac pathway.
The c-jun proto-oncogene encodes a transcription factor which is activated by mitogens both transcriptionally and by phosphorylation by Jun N-terminal kinase (JNK). We have investigated the cellular signalling pathways involved in epidermal growth factor (EGF) induction of the c-jun promoter. We find that two sequence elements, which bind ATF1 and MEF2D transcription factors, are required in HeLa cells, although they are not sufficient for maximal induction. Activated forms of Ras, RacI, Cdc42Hs, and MEKK increased expression of the c-jun promoter, while dominant negative forms of Ras, RacI, and MEK kinase (MEKK) inhibited EGF induction. These and previously published results suggest that EGF activates the c-jun promoter by a Ras-to-Rac-to-MEKK pathway. This pathway is similar to that used for posttranslational activation of c-jun by JNK.
Clarke
N
N
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
Arenzana
N
N
Hai
T
T
Minden
A
A
Prywes
R
R
D051697:Activating Transcription Factor 1; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D026161:MADS Domain Proteins; D048728:MAP Kinase Kinase Kinase 1; D064326:MEF2 Transcription Factors; D020928:Mitogen-Activated Protein Kinases; D018006:Myogenic Regulatory Factors; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D051057:Proto-Oncogene Proteins c-akt; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein
D051697:Activating Transcription Factor 1; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D026161:MADS Domain Proteins; C000715470:MAS1 protein, human; D064326:MEF2 Transcription Factors; C578043:MEF2D protein, human; D018006:Myogenic Regulatory Factors; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D004815:Epidermal Growth Factor; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human; D019204:GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein