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 of IL-4 binding to its receptor. Molecular characterization of IL-4NAF by ultraviolet light cross-linking experiments revealed a single protein of 120-130 kDa in contact with the DNA target site. Glycerol gradient sedimentation analysis indicated a molecular mass of IL-4 NAF consistent with a monomer that is capable of binding DNA. The IL-4 NAF target site is a palindromic sequence that is also recognized by the interferon-induced transcription factor, p91/STAT1 alpha. However, IL-4 NAF and p91/STAT1 alpha display distinguishable DNA binding specificities that may generate one level of specificity in the expression of target genes. Previous studies suggested the involvement of the insulin receptor substrate-1 (IRS-1) in the IL-4 signal transduction pathway. Although IRS-1 is involved in the stimulation of mitogenesis, our results demonstrate that activation of IL-4 NAF is independent of IRS-signaling proteins. The results of this study indicate that IL-4 stimulates bifurcating signal pathways that can direct mitogenesis via the IRS-signaling proteins and specific gene expression via the IL-4 NAF.
Kotanides
H
H
Graduate Program in Molecular and Cellular Biology, State University of New York, Stony Brook 11794-8691, USA.
Moczygemba
M
M
White
M F
MF
Reich
N C
NC
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D015847:Interleukin-4 / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; C087516:NF-IL4 protein, human; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D015847:Interleukin-4