Fig. 1

Interferon-γ signaling. Canonical IFN-γ signaling pathway requires activation of its receptor, IFN-γ receptor (IFNGR) and consequent, stimulation of JAK/STAT (Janus kinase/signal transducers and activators of transcription) signaling. The binding of IFN-γ to the IFNGR complex results in tight association of IFNGR1 and IFNGR2 and a reorientation of their intracellular domains. Close association of JAK1 and JAK2 proteins facilitate auto- and transphosphorylation and enzymatic activation. Furthermore, activated JAK proteins phosphorylate the STAT1 binding site, activating his dimerization and translocation to the nucleus where it binds to γ-activated site (GAS) elements and promotes gene transcription. The JAK-STAT pathway is negatively regulated at multiple sites: SOCS suppresses JAK and STAT activation, while PIAS inhibits IFN-γ induced gene transcription. In a non-canonical pathway, IFN-γ stimulates STAT1-PI3K-Akt axis what leads to implication of mammalian target of rapamycin (mTOR) in interferon signaling. Furthermore, mTOR/p70S6 kinase cascade promotes mRNA translation of effector proteins