Dose-dependent activation of p21ras by IFN-beta

Recent studies have demonstrated that interferon-beta (IFN-beta) activates extracellular regulated kinases (ERKs) in myeloma cells and have revealed a link between ERKs and the Jak/Stat pathway. The upstream components of the IFN-beta pathway involved in activation of ERKs are unknown. As p21ras is often an upstream component of the ERK pathway, we have investigated p21ras activity following IFN-beta treatment of the human myeloma cell line, U266. IFN-beta was found to strongly activate p21ras at relatively low doses and to exert a negative effect at the higher doses normally employed in signaling studies. There was no direct correlation between p21ras and ERK activity, suggesting that p21ras plays an alternate role in the IFN-beta signaling pathway. These results imply a unique integration of p21ras signaling within the milieu of IFN-induced cytoplasmic signaling events.