title: Requirement for MAP kinase (ERK2) activity in interferon alpha- and interferon beta-stimulated gene expression through STAT proteins.
abstract: Activation of early response genes by interferons (IFNs) requires tyrosine phosphorylation of STAT (signal transducers and activators of transcription) proteins. It was found that the serine-threonine kinase mitogen-activated protein kinase (MAPK) [specifically, the 42-kilodalton MAPK or extracellular signal-regulated kinase 2 (ERK2)] interacted with the alpha subunit of IFN-alpha/beta receptor in vitro and in vivo. Treatment of cells with IFN-beta induced tyrosine phosphorylation and activation of MAPK and caused MAPK and Stat1 alpha to coimmunoprecipitate. Furthermore, expression of dominant negative MAPK inhibited IFN-beta-induced transcription. Therefore, MAPK appears to regulate IFN-alpha and IFN-beta activation of early response genes by modifying the Jak-STAT signaling cascade.
authors.affiliation: Division of Cytokine Biology, Center for Biologics Evaluation and Research, Bethesda, MD 20892, USA.
authors.forename: M
authors.initials: M
authors.lastname: David
authors.forename: E
authors.initials: E
authors.lastname: Petricoin
authors.forename: C
authors.initials: C
authors.lastname: Benjamin
authors.forename: R
authors.initials: R
authors.lastname: Pine
authors.forename: M J
authors.initials: MJ
authors.lastname: Weber
authors.forename: A C
authors.initials: AC
authors.lastname: Larner
mesh_terms: D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology*; D008565:Membrane Proteins; D019950:Mitogen-Activated Protein Kinase 1; D010766:Phosphorylation; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D008565:Membrane Proteins; D017471:Receptors, Interferon; D011993:Recombinant Fusion Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D053633:Receptor, Interferon alpha-beta; D014443:Tyrosine; D016899:Interferon-beta; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1