Figure 4. Complexity of the signalling response.

Different types of cells respond differentially to a single type of interferon (IFN) by varying the activation of specific signal transducers and activators of transcription (STATs), additional transcription factors (TFs) and kinases in addition to the Janus kinases (JAKs). Priming of cells by pre-treatment with another cytokine modulates the response further by increasing the amounts of negative regulators and by modulating other processes. Most genes require STATs, with or without additional TFs, and several genes respond only to activated TFs and not to STATs. The STATs bind to IFN-γ-activated site (GAS) elements or, together with IFN regulatory factor (IRF) proteins, to IFN-stimulated response elements (ISREs), and the TFs bind to specific binding elements (TFBE). CIS, cytokine inducible SH2-containing protein; PTP, protein tyrosine phosphatase; SOCS1, suppressor of cytokine signalling 1.