Stress-induced immediate-early gene, egr-1, involves activation of p38/JNK1.
The Ras/Raf/MAP kinase (ERK) pathway is a major signaling pathway induced by growth factors in mammalian cells. Two other types of mammalian MAP kinases, JNK (SAPK) and p38 (RK, CSBP), are induced by environmental stress. Although the immediate-early gene, egr-1, is induced by growth factors, cytokines, differentiation signals and DNA damaging agents, less is known about its induction by environmental stress and the mechanism involved. Here we report that in NIH3T3 cells, egr-1 is induced by various stress treatments such as heat shock, sodium arsenite, ultraviolet (U.V.) radiation, and anisomycin. p38 and JNK1, but not ERK2, were activated by these stress treatments. Induction of egr-1 by anisomycin is inhibited by a specific inhibitor of p38, SB 203580. We also show that p38 and JNK1 activated by their upstream kinases induce egr-1 promoter activity through activation of the ternary complex factor, Elk-1. The stress treatments also lead to an increase in Egr-1 protein phosphorylation and its DNA binding activity. Together, our data suggest that induction of egr-1 gene by growth factors and stress are mediated through different subgroups of MAP kinases which may also differentially affect egr-1 function on its target genes.
Signal Transduction Laboratory, Institute of Molecular and Cell Biology, National University of Singapore, Singapore.
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D016475:3T3 Cells; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D018053:Arsenites / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051766:Early Growth Response Protein 1; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000528:radiation effects*; D018869:Heat-Shock Response; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D017874:Immediate-Early Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D020928:Mitogen-Activated Protein Kinases; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger; D017670:Sodium Compounds / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014466:Ultraviolet Rays; D050807:ets-Domain Protein Elk-1; D048051:p38 Mitogen-Activated Protein Kinases
D018053:Arsenites; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; C494112:ELK1 protein, human; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; C494113:Elk1 protein, mouse; D004791:Enzyme Inhibitors; D007093:Imidazoles; D017874:Immediate-Early Proteins; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D011725:Pyridines; D012333:RNA, Messenger; D017670:Sodium Compounds; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; C017947:sodium arsenite; D000841:Anisomycin; D004247:DNA; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580