Dose-Dependent Activation of p21 ras by IFN-β

Abstract

Recent studies have demonstrated that interferon-β (IFN-β) 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-β pathway involved in activation of ERKs are unknown. As p21^ras is often an upstream component of the ERK pathway, we have investigated p21^ras activity following IFN-β treatment of the human myeloma cell line, U266. IFN-β was found to strongly activate p21^ras 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 p21^ras and ERK activity, suggesting that p21^ras plays an alternate role in the IFN-β signaling pathway. These results imply a unique integration of p21^ras signaling within the milieu of IFN-induced cytoplasmic signaling events.