Requirement for MAP Kinase (ERK2) Activity in Interferon α- and Interferon β-Stimulated Gene Expression Through STAT Proteins

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 α subunit of IFN-α/β receptor in vitro and in vivo. Treatment of cells with IFN-β induced tyrosine phosphorylation and activation of MAPK and caused MAPK and Stat1α to coimmunoprecipitate. Furthermore, expression of dominant negative MAPK inhibited IFN-β-induced transcription. Therefore, MAPK appears to regulate IFN-α and IFN-β activation of early response genes by modifying the Jak-STAT signaling cascade.