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
展开▼
机译：干扰素-γ信号传导。规范IFN-γ信号传导途径需要激活其受体，IFN-γ受体（IFNGR）并因此刺激Jak / Stat（Janus激酶/信号传感器和转录激活剂）信号传导。 IFN-γ对IFNGR复合物的结合导致IFNGR1和IFNGR2的紧密关联和它们的细胞内域的重新定位。 Close jak1和Jak2蛋白的关联促进了自动和转磷酸化和酶活化。此外，活化的jak蛋白磷酸化attat1结合位点，使其与核的二聚化和易位激活，其中与γ-活化位点（气体）元素结合并促进基因转录。 Jak-Stat途径在多个站点进行负面调节：SOC抑制JAK和STAT激活，而PIS抑制IFN-γ诱导的基因转录。在非规范途径中，IFN-γ刺激STAT1-PI3K-AKT轴，导致在干扰素信号中催化雷帕霉素（MTOR）的哺乳动物靶标。此外，MTOR / P70S6激酶级联促进了效应蛋白的mRNA翻译
展开▼
