CHARACTERIZATION OF THE INTERLEUKIN-4 NUCLEAR ACTIVATED FACTOR STAT AND ITS ACTIVATION INDEPENDENT OF THE INSULIN-RECEPTOR SUBSTRATE PROTEINS/

The activation of a latent DNA binding factor by interleukin-4 (IL-4), the IL-4 nuclear activated factor (IL-4 NAF), occurs within minutes o f IL-4 binding to its receptor. Molecular characterization of IL-4 NAF by ultraviolet light cross-linking experiments revealed a single prot ein of 120-130 kDa in contact with the DNA target site. Glycerol gradi ent sedimentation analysis indicated a molecular mass of IL-4 NAF cons istent with a monomer that is capable of binding DNA. The IL-4 NAF tar get site is a palindromic sequence that is also recognized by the inte rferon-induced transcription factor, p91/STAT1 alpha. However, IL-4 NA F and p91/STAT1 alpha display distinguishable DNA binding specificitie s that may generate one level of specificity in the expression of targ et genes. Previous studies suggested the involvement of the insulin re ceptor substrate-1 (IRS-1) in the IL-4 signal transduction pathway. Al though IRS-1 is involved in the stimulation of mitogenesis, our result s demonstrate that activation of IL-4 NAF is independent of IRS-signal ing proteins. The results of this study indicate that IL-4 stimulates bifurcating signal pathways that can direct mitogenesis via the IRS-si gnaling proteins and specific gene expression via the IL-4 NAF.