A novel internalization motif regulates human IFN-? R1 endocytosis.

ABSTRACT: This study tested the hypothesis that the IFN-? R1 287-YVSLI-91 intracellular motif regulates its endocytosis. IFN-? exerts its biological activities by interacting with a specific cell-surface RC composed of two IFN-? R1 and two IFN-? R2 chains. Following IFN-? binding and along with the initiation of signal transduction, the ligand and IFN-? 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-? R1-deficient fibroblasts with WT and site-directed, mutagenesis-generated mutant IFN-? R1 expression vectors helped us to identify region IFN-? R1 287-YVSLI-291 as the critical domain required for IFN-?-induced IFN-? 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-? Rs across species. The IFN-? R1 270-LI-271 dileucine motif, previously thought to be involved in this receptor endocytosis, showed to be unnecessary for receptor endocytosis.

SUBMITTER: Yancoski J 

PROVIDER: S-EPMC3395421 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature