| A novel internalization motif regulates human IFN-γ R1 endocytosis. | |
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MedLine Citation:
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PMID: 22595141 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Judith Yancoski; Mohammed A Sadat; Nadia Aksentijevich; Andrea Bernasconi; Steven M Holland; Sergio D Rosenzweig |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural Date: 2012-05-17 |
Journal Detail:
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Title: Journal of leukocyte biology Volume: 92 ISSN: 1938-3673 ISO Abbreviation: J. Leukoc. Biol. Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-08-01 Completed Date: 2012-09-17 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 8405628 Medline TA: J Leukoc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 301-8 Citation Subset: IM |
Affiliation:
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Servicio de Inmunología y Reumatología, Hospital Nacional de Pediatría J. P. Garrahan, Buenos Aires, Argentina. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Motifs
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immunology Amino Acid Sequence Conserved Sequence / immunology Endocytosis / immunology* HEK293 Cells Humans Leucine / chemistry*, metabolism* Molecular Sequence Data Protein Sorting Signals / physiology Receptors, Interferon / chemistry*, genetics, metabolism* Tyrosine / chemistry, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01TW006644/TW/FIC NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Protein Sorting Signals; 0/Receptors, Interferon; 0/interferon gamma receptor; 55520-40-6/Tyrosine; 61-90-5/Leucine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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