title: Neither ERK nor JNK/SAPK MAP kinase subtypes are essential for histone H3/HMG-14 phosphorylation or c-fos and c-jun induction.
abstract: The effects of EGF, TPA, UV radiation, okadaic acid and anisomycin on ERK and JNK/SAPK MAP kinase cascades have been compared with their ability to elicit histone H3/HMG-14 phosphorylation and induce c-fos and c-jun in C3H 10T1/2 cells. EGF and UV radiation activate both ERKs and JNK/SAPKs but to markedly different extents; EGF activates ERKs more strongly than JNK/SAPKs, whereas UV radiation activates JNK/SAPKs much more strongly than ERKs. Anisomycin and okadaic acid activate JNK/SAPKs but not ERKs, and conversely, TPA activates ERKs but not JNK/SAPKs. Nevertheless, all these agents elicit phosphorylation of ribosomal and pre-ribosomal S6, histone H3 and HMG-14, and the induction of c-fos and c-jun, showing that neither cascade is absolutely essential for these responses. We then analysed the relationship between ERKs, JNK/SAPKs and the transcription factors Elk-1 and c-Jun, implicated in controlling c-fos and c-jun, respectively. JNK/SAPKs bind to GST-cJun1-79, and ERKs, particularly ERK-2, to GST-Elk1(307-428); there is no cross-specificity of binding. Further, GST-Elk1(307-428) binds preferentially to active rather than inactive ERK-2. In vitro, JNK/SAPKs phosphorylate both GST-cJun1-79 and GST-Elk1(307-428), whereas ERKs phosphorylate GST-Elk1(307-428) but not GST-cJun1-79. Thus, neither ERKs nor JNK/SAPKs are absolutely essential for nuclear signalling and c-fos and c-jun induction. The data suggest either that activation of a single MAP kinase subtype is sufficient to elicit a complete nuclear response, or that other uncharacterised routes exist.
authors.affiliation: Nuclear Signalling Laboratory, Randall Institute, King's College London, UK.
authors.forename: E
authors.initials: E
authors.lastname: Cano
authors.forename: C A
authors.initials: CA
authors.lastname: Hazzalin
authors.forename: E
authors.initials: E
authors.lastname: Kardalinou
authors.forename: R S
authors.initials: RS
authors.lastname: Buckle
authors.forename: L C
authors.initials: LC
authors.lastname: Mahadevan
mesh_terms: D016475:3T3 Cells / Q000201:enzymology; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002467:Cell Nucleus / Q000502:physiology / Q000528:radiation effects; D002843:Chromatin / Q000378:metabolism / Q000528:radiation effects; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D005786:Gene Expression Regulation; D017781:Genes, Immediate-Early / Q000502:physiology; D016762:Genes, fos / Q000235:genetics; D016758:Genes, jun / Q000235:genetics; D006609:High Mobility Group Proteins / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D007527:Isoenzymes / Q000502:physiology; D048670:MAP Kinase Kinase 4; D051379:Mice; D008809:Mice, Inbred C3H; D020929:Mitogen-Activated Protein Kinase Kinases; D019319:Okadaic Acid; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D013379:Substrate Specificity; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors; D014466:Ultraviolet Rays; D050807:ets-Domain Protein Elk-1
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; C494113:Elk1 protein, mouse; D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D006609:High Mobility Group Proteins; D006657:Histones; D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D019319:Okadaic Acid; D004815:Epidermal Growth Factor; D000841:Anisomycin; D011494:Protein Kinases; D020794:Receptor Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048670:MAP Kinase Kinase 4; C482562:Map2k4 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases; D013755:Tetradecanoylphorbol Acetate