REQUIREMENT FOR MAP KINASE (ERK2) ACTIVITY IN INTERFERON-ALPHA-STIMULATED AND INTERFERON-BETA-STIMULATED GENE-EXPRESSION THROUGH STAT PROTEINS

Activation of early response genes by interferons (IFNs) requires tyro sine phosphorylation of STAT (signal transducers and activators of tra nscription) proteins. It was found that the serine-threonine kinase mi togen-activated protein kinase (MAPK) [specifically, the 42-kilodalton MAPK or extracellular signal-regulated kinase 2 (ERK2)] interacted wi th 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 coimmunoprecipit ate. Furthermore, expression of dominant negative MAPK inhibited IFN-b eta-induced transcription. Therefore, MAPK appears to regulate IFN-alp ha and IFN-beta activation of early response genes by modifying the Ja k-STAT signaling cascade.