The stat proteins function both as cytoplasmic signal transducers and as activators of transcription. Stat1 is expressed as two variants of 84 and 91 kDa. Stat1 proteins contain SH2 and SH3 domains, and are components of the interferon-stimulated gene factor 3 (ISGF3) complex. This complex is the primary transcription activator induced by the binding of interferon to its receptors. In response to activation by various cytokines and growth factors, stat1 subunits become phosphorylated at tyrosine 701. This leads to translocation of stat1 to the nucleus, resulting in formation of an active ISGF3 complex. Active ISGF3 modulates the transcription of the interferon-stimulated genes. Thus, phosphorylation of Tyr-701 is critical for gene expression mediated by various cytokines and growth factors.