In mid-1980s, it was shown that the genes that respond to interferon carry a common regulator sequence called ISRE (interferon stimulated response element). In late 1980s, the transcription factor that binds to ISRE was also discovered. This transcription factor consists of four protein subunits including three large subunits, and a small subunit. The fourth small subunit actually makes contact with the ISRE. It was also shown that the three large subunits of the transcription factor, each contains an SH2 domain, a sequence commonly found in proteins that interact with tyrosine kinase.

In cells, which have not been stimulated by interferon-a, the three large subunits of the above transcription factor, are not linked and are located only in the cytoplasm. But once interferon-α binds to its receptor, these three subunits rapidly undergo phosphorylation at the tyrosine residues due to tyrosine kinase associated with the receptor. The phosphorylated protein subunits associate together and move to the nucleus, where they join the smaller subunit to make the active transcription factor, thus conferring on it the ability to bind on ISRE. This leads to interferon-α stimulated expression of specific genes (Fig. 37.26).