Noncanonical IFN Signaling, Steroids, and STATs: A Probable Role of V-ATPase

Figure 2

Schematic of IFNγ binding to the receptor subunit IFNGR1 extracellular domain with endocytosis of the complex and subsequent movement of IFNγ to the cytoplasmic domain of IFNGR1 at a site encompassing residues 253 to 287. Endosome-associated V-ATPase proton pump lowers the lumen pH for IFNγ movement to the cytosol. Accordingly, extracellular binding of ¹²⁵I–IFNγ is blocked by unlabeled IFNγ but not peptide IFNGR1(253-287). Cytoplasmic binding of ¹²⁵I–IFNγ is blocked by IFNGR1(253-287). Details of the experiment illustrated in this schematic are contained in the text [32]. Similar movement for ligands of RTKs from the receptor extracellular domain to the cytoplasm of the cell has been shown [15].