A DIRECT SIGNALING PATHWAY THROUGH TYROSINE KINASE ACTIVATION OF SH2 DOMAIN-CONTAINING TRANSCRIPTION FACTORS

Studies on the mechanism of interferon-induced gene expression revealed a direct signaling pathway from cell surface receptors to transcription factors. In this pathway, signal transduction is mediated by a new class of transcription factor STAT (signal transducer and activator of transcription). We have shown that STAT factors contain Src homolopy region 2 and 3 domains and are phosporylated and activated in the cytoplasm by receptor associated tyrosine kinases. The activated transcription factors then translocate to the nucleus, joined by a nuclear DNA binding factor, to form an active transcriptional complex. Recent studies have shown that this direct signaling pathway is the key to control of gene expression induced by many cytokines and growth factors.