Table 1.
An overview of non-canonical Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signaling by components of interferon (IFN) pathways.
| Genotype | Non-canonical STAT complexes | Function |
|---|---|---|
| WT overexpressing IFN-stimulated gene factor 3 (ISGF3) subunits | Unphosphorylated ISGF3 complex | Prolonged IFN-I responses, resistance to DNA damage |
| WT expressing high levels of STAT2 | pYSTAT1/U-STAT2 | Inhibition of STAT1 nuclear translocation, quenching of IFNγ response |
| STAT1Y701F | STAT1Y701F/STAT2/? | Inhibition of STAT2 nuclear translocation, quenching of type I IFN response |
| STAT1Y701F/? | Natural killer (NK) cytotoxicity | |
| STAT1S727A | STAT1S727A dimer | Reduction of IFNγ response |
| STAT1S727A/? | NK cytotoxicity | |
| STAT1−/− | STAT2/interferon regulatory factor 9 (IRF9) | Flavivirus and Legionella pneumophila resistance |
| STAT2−/− | STAT1/IRF9 | IFNγ—colitis, IFN-I—Legionella pneumophila resistance |
| TYK2K923E | – | NK cytotoxicity, mitochondrial respiration, IFNAR stability (in humans) |
| JAK2KD | – | IFN-gamma receptor stability, residual IFNγ response |
“?” represents unknown interactors.