| First Author | Xu X | Year | 2018 |
| Journal | Cell | Volume | 175 |
| Issue | 5 | Pages | 1336-1351.e17 |
| PubMed ID | 30318148 | Mgi Jnum | J:267413 |
| Mgi Id | MGI:6259272 | Doi | 10.1016/j.cell.2018.09.011 |
| Citation | Xu X, et al. (2018) Phosphorylation-Mediated IFN-gammaR2 Membrane Translocation Is Required to Activate Macrophage Innate Response. Cell 175(5):1336-1351.e17 |
| abstractText | As a critical step during innate response, the cytoplasmic beta subunit (IFN-gammaR2) of interferon-gamma receptor (IFN-gammaR) is induced and translocates to plasma membrane to join alpha subunit to form functional IFN-gammaR to mediate IFN-gamma signaling. However, the mechanism driving membrane translocation and its significance remain largely unknown. We found, unexpectedly, that mice deficient in E-selectin, an endothelial cell-specific adhesion molecule, displayed impaired innate activation of macrophages upon Listeria monocytogenes infection yet had increased circulating IFN-gamma. Inflammatory macrophages from E-selectin-deficient mice had less surface IFN-gammaR2 and impaired IFN-gamma signaling. BTK elicited by extrinsic E-selectin engagement phosphorylates cytoplasmic IFN-gammaR2, facilitating EFhd2 binding and promoting IFN-gammaR2 trafficking from Golgi to cell membrane. Our findings demonstrate that membrane translocation of cytoplasmic IFN-gammaR2 is required to activate macrophage innate response against intracellular bacterial infection, identifying the assembly of functional cytokine receptors on cell membrane as an important layer in innate activation and cytokine signaling. |
