Document Detail

A novel internalization motif regulates human IFN-γ R1 endocytosis.
MedLine Citation:
PMID:  22595141     Owner:  NLM     Status:  MEDLINE    
This study tested the hypothesis that the IFN-γ R1 287-YVSLI-91 intracellular motif regulates its endocytosis. IFN-γ exerts its biological activities by interacting with a specific cell-surface RC composed of two IFN-γ R1 and two IFN-γ R2 chains. Following IFN-γ binding and along with the initiation of signal transduction, the ligand and IFN-γ 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-γ R1-deficient fibroblasts with WT and site-directed, mutagenesis-generated mutant IFN-γ R1 expression vectors helped us to identify region IFN-γ R1 287-YVSLI-291 as the critical domain required for IFN-γ-induced IFN-γ 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-γ Rs across species. The IFN-γ R1 270-LI-271 dileucine motif, previously thought to be involved in this receptor endocytosis, showed to be unnecessary for receptor endocytosis.
Judith Yancoski; Mohammed A Sadat; Nadia Aksentijevich; Andrea Bernasconi; Steven M Holland; Sergio D Rosenzweig
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural     Date:  2012-05-17
Journal Detail:
Title:  Journal of leukocyte biology     Volume:  92     ISSN:  1938-3673     ISO Abbreviation:  J. Leukoc. Biol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-01     Completed Date:  2012-09-17     Revised Date:  2013-08-14    
Medline Journal Info:
Nlm Unique ID:  8405628     Medline TA:  J Leukoc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  301-8     Citation Subset:  IM    
Servicio de Inmunología y Reumatología, Hospital Nacional de Pediatría J. P. Garrahan, Buenos Aires, Argentina.
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MeSH Terms
Amino Acid Motifs / immunology
Amino Acid Sequence
Conserved Sequence / immunology
Endocytosis / immunology*
HEK293 Cells
Leucine / chemistry*,  metabolism*
Molecular Sequence Data
Protein Sorting Signals / physiology
Receptors, Interferon / chemistry*,  genetics,  metabolism*
Tyrosine / chemistry,  metabolism
Grant Support
Reg. No./Substance:
0/Protein Sorting Signals; 0/Receptors, Interferon; 0/interferon gamma receptor; 55520-40-6/Tyrosine; 61-90-5/Leucine

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