Interferon Gamma Receptor: The Beginning of the Journey

Abstract

Our view of endocytosis and membrane trafficking of transmembrane receptors has dramatically changed over the last 20 years. Several new endocytic routes have been discovered and mechanistically characterized in mammalian cells. Long considered as a passive means to terminate signaling through down-regulation of the number of activated receptors at the plasma membrane, it is now established that receptor endocytosis and endosomal sorting can be directly linked to the regulation of intracellular signaling pathways. The functional links between membrane trafficking of interferon receptors and JAK/STAT signaling have recently begun to be unraveled. These studies raise the exciting possibility that a certain level of signal specificity can be achieved through endocytosis and selective localization of the activated complexes within cellular membranes. The ongoing development of high-resolution cell imaging techniques with better spatial and temporal resolution gives new means of deciphering the inherent complexity of membrane trafficking and signaling. This should help to better comprehend the molecular mechanisms by which endocytosis and endosomal sorting of interferon receptors can orchestrate signaling selectivity within the JAK/STAT pathway that can be activated by as many as 60 different cytokines, growth factors, and hormones.

Bilberry-Derived Anthocyanins Prevent IFN-γ-Induced Pro-Inflammatory Signalling and Cytokine Secretion in Human THP-1 Monocytic Cells

“…It is well known that inflammatory pathways induced by IFN-γ and TNF-α play a central role in IBD pathogenesis [29]. IFN-γ effects are elicited through activation of intracellular signalling pathways like the JAK-STAT pathway [30]. This pathway leads to STAT1 phosphorylation resulting in target gene expression.…”

Toxoplasma gondii Inhibits Gamma Interferon (IFN-γ)- and IFN-β-Induced Host Cell STAT1 Transcriptional Activity by Increasing the Association of STAT1 with DNA

“…However, when IFN-␥ is removed its signaling pathway is downregulated through dephosphorylation of the JAKs and internalization of the IFN-␥ receptor (43,46). To determine how quickly the IFN-␥ pathway is deactivated after IFN-␥ is removed, we stimulated HFFs on coverslips with IFN-␥ for 30 min, washed the IFN-␥ away, fixed the cells after either 3.5 or 21.5 h, and quantified the nuclear accumulation of phospho-STAT1…”

Targeting Jurkat T Lymphocyte Leukemia Cells by an Engineered Interferon-Alpha Hybrid Molecule

“…IFNα binds to its surface receptor and initiates a cascade of events that induces the phosphorylation of JAK1 and TYK2 kinases, followed by the activation of the signal transducer and activation of transcription (STAT) family transcription factors [34,35]. After activation, the STAT complex is subsequently translocated to the nucleus, where it induces transcription of genes related to cell-cycle arrest and apoptosis [36,37]. In this study, we demonstrate that the Jurkat-binding peptide promotes the binding of IFNα to the membrane receptor (Fig.…”