Contribution of MAP kinase pathways to the activation of ATF-2 in human neuroblastoma cells.
Activated Transcription Factor-2 (ATF-2) is important during development of and during injury to the brain. Both Jun N-terminal Kinases (JNKs) and p38 Mitogen-Activated Protein Kinases (p38MAPKs) may phosphorylate ATF-2, but the contribution of these two pathways in cells has never been investigated. We have assayed endogenous p38MAPK activity in SK-N-MC and SH-SY5Y human neuroblastoma cells for activation of a GAL4/ATF-2 fusionprotein, by means of titrations of transfected expression plasmids and by using the p38MAPK inhibitor SB203580. It was found that basal activation of ATF-2 was independent of p38MAPK and that whereas MAPK kinase-3 (MKK3) was a weak inducer of ATF-2 activation, it was a potent activator of the stress activated transcription factor CHOP. In contrast, ATF-2 was very potently activated by the JNK pathway activator MAPK kinase kinase-1 (MEKK1). Thus, kinases downstream of MEKK1 appear relevant, but it is unlikely that p38MAPKs contribute quantitatively to activation of ATF-2 in these cells.
Tindberg
N
N
Institute of Environmental Medicine, Division of Molecular Toxicology, Karolinska Institutet, Stockholm, Sweden. nictin@ki.se
Porsmyr-Palmertz
M
M
Simi
A
A
D051698:Activating Transcription Factor 2; D022762:CCAAT-Enhancer-Binding Proteins; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics; D018628:Gene Dosage; D017930:Genes, Reporter; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D048371:MAP Kinase Kinase 3; D048728:MAP Kinase Kinase Kinase 1; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009447:Neuroblastoma / Q000201:enzymology* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D010957:Plasmids / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D029701:Saccharomyces cerevisiae Proteins; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D022762:CCAAT-Enhancer-Binding Proteins; D017362:Cyclic AMP Response Element-Binding Protein; C497249:DDIT3 protein, human; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D007093:Imidazoles; D011725:Pyridines; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D051742:Transcription Factor CHOP; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human; D048371:MAP Kinase Kinase 3; C482530:MAP2K3 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; C093642:SB 203580