A novel internalization motif regulates human IFN-gamma R1 endocytosis

作者：Yancoski Judith; Sadat Mohammed A; Aksentijevich Nadia; Bernasconi Andrea; Holland Steven M; Rosenzweig Sergio D^*

来源：Journal of Leukocyte Biology, 2012, 92(2): 301-308.

DOI：10.1189/jlb.0212057

• tyrosine-based endocytosis motifs
• dileucine-based endocytosis motifs
• recycling
• transmembrane proteins

This study tested the hypothesis that the IFN-gamma R1 287-YVSLI-91 intracellular motif regulates its endocytosis. IFN-gamma exerts its biological activities by interacting with a specific cell-surface RC composed of two IFN-gamma R1 and two IFN-gamma R1 chains. Following IFN-gamma binding and along with the initiation of signal transduction, the ligand and IFN-gamma R1 are internalized. Two major types of consensus-sorting signals are described in receptors, which are rapidly internalized from the plasma membrane to intracellular compartments: tyrosine-based and dileucine-based internalization motifs. Transfection of HEK 293 cells and IFN-gamma R1-deficient fibroblasts with WT and site-directed, mutagenesis-generated mutant IFN-gamma R1 expression vectors helped us to identify region IFN-gamma R1 287-YVSLI-291 as the critical domain required for IFN-gamma-induced IFN-gamma R1 internalization and Y287 and LI290-291 as part of a common structure essential for receptor endocytosis and function. This new endocytosis motif, YxxLI, shares characteristics of tyrosine-based and dileucine-based internalization motifs and is highly conserved in IFN-gamma Rs across species. The IFN-gamma R1 270-LI-271 dileucine motif, previously thought to be involved in this receptor endocytosis, showed to be unnecessary for receptor endocytosis. J. Leukoc. Biol. 92: 301-308; 2012.

• 出版日期2012-8