IFN-alpha activates Stat6 and leads to the formation of Stat2:Stat6 complexes in B cells.
IFN-alpha consists of a family of highly homologous proteins, which exert pleiotropic effects on a wide variety of cell types. The biologic activities of IFN-alpha are mediated by its binding to a multicomponent receptor complex resulting in the activation of the Janus kinase-STAT signaling pathway. In most cell types, activation of Stat1 and Stat2 by IFN-alpha leads to the formation of either STAT homo-/heterodimers or of the IFN-stimulated gene factor 3 complex composed of Stat1, Stat2, and p48, a non-STAT protein. These distinct transcriptional complexes then target two different sets of cis-elements, gamma-activated sites and IFN-stimulated response elements. Here, we report that IFN-alpha can activate complexes containing Stat6, which, until now, has been primarily associated with signaling by two cytokines with biologic overlap, IL-4 and IL-13. Induction of Stat6 complexes by IFN-alpha appears to be cell type specific, given that tyrosine phosphorylation of Stat6 in response to IFN-alpha is predominantly detected in B cells. Activation of Stat6 by IFN-alpha in B cells is accompanied by the formation of novel Stat2:Stat6 complexes, including an IFN-stimulated gene factor 3-like complex containing Stat2, Stat6, and p48. B cell lines resistant to the antiproliferative effects of IFN-alpha display a decrease in the IFN-alpha-mediated activation of Stat6. Activation of Stat6 as well as of Stat2:Stat6 complexes by IFN-alpha in B cells may allow modulation of target genes in a cell type-specific manner.
Pubmed ID: 10490982 RIS Download
B-Lymphocytes | DNA-Binding Proteins | Drug Resistance, Neoplasm | Humans | Interferon Regulatory Factor-1 | Interferon-alpha | Lymphocyte Activation | Macromolecular Substances | Phosphoproteins | Protein Binding | STAT2 Transcription Factor | STAT6 Transcription Factor | Trans-Activators | Tumor Cells, Cultured