Functional divergence of the MAP kinase pathway. ERK1 and ERK2 activate specific transcription factors.
Growth factor-receptor interactions at the cell surface eventually leading to the transcriptional activation of immediate early genes is mediated by the mitogen-activated protein kinase (MAP kinase/MAPK) cascade. Here we show that overexpression of extracellular signal-regulated kinase 1 (ERK1) cDNA, encoding p44mapk, results in the activation of Elk-1, the serum response factor accessory protein. We also show that overexpression of ERK2, encoding p42mapk, activates Myc, but not Elk-1. Therefore, the MAP kinase cascade diverges with at least one specific target for each MAP kinase isoform and provides a novel mechanism for differential regulation of this signaling pathway.
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, ROC.
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D016475:3T3 Cells; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins; D015870:Gene Expression; D006801:Humans; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D008980:Moloney murine sarcoma virus / Q000235:genetics; D010766:Phosphorylation; D010957:Plasmids; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D051381:Rats; D012091:Repetitive Sequences, Nucleic Acid; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection; D050807:ets-Domain Protein Elk-1
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C494112:ELK1 protein, human; C494113:Elk1 protein, mouse; C494114:Elk1 protein, rat; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D008668:Metallothionein; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases