Document Detail


Internalization and intracellular fate of TCR-CD3 complexes.
MedLine Citation:
PMID:  11100805     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The number of surface TCR-CD3 complexes is maintained by an equilibrium between the synthesis and secretion of new polypeptides, their internalization, recycling, and degradation. The different subunits of the TCR-CD3 complex do not display the same intracellular trafficking dynamics. Thus, in the absence of stimuli, TCR and zeta chains may be degraded at a higher rate than CD3 subunits, which are mostly recycled. T-cell activation by antigen, anti-TCR-CD3 antibodies, or pharmacological activators of protein kinase C, results in increased TCR-CD3 internalization, followed by the downmodulation of TCR-CD3 surface levels. Once internalized, TCR-CD3 complexes may either enter a recycling pathway or be sorted to lysosomes and degraded. Protein serine kinases and protein tyrosine kinases may influence the internalization and intracellular sorting of TCR-CD3 complexes. In line with these results TCR-CD3 ligands stimulate both TCR-CD3 internalization and degradation, whereas protein kinase C activators stimulate internalization only. Depending on the stimulus applied, internalization motifs from one or several TCR-CD3 subunits mediate endocytic routing of the complex. The involvement of signaling molecules in the intracellular fate of TCR-CD3, the nature and location of sequences for internalization and intracellular sorting, and the role of downregulation in T-cell activation are still the main open questions.
Authors:
A Alcover; B Alarcón
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Critical reviews in immunology     Volume:  20     ISSN:  1040-8401     ISO Abbreviation:  Crit. Rev. Immunol.     Publication Date:  2000  
Date Detail:
Created Date:  2001-03-06     Completed Date:  2001-05-31     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8914819     Medline TA:  Crit Rev Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  325-46     Citation Subset:  IM    
Affiliation:
Unité de Biologie des Interactions Cellulaires, CNRS, URA 1960, Institut Pasteur, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Down-Regulation
Endocytosis
Half-Life
Humans
Lymphocyte Activation
Phosphorylation
Protein Kinase C / physiology
Receptor-CD3 Complex, Antigen, T-Cell / metabolism*
Serine / metabolism
Signal Transduction
T-Lymphocytes / metabolism
Chemical
Reg. No./Substance:
0/Receptor-CD3 Complex, Antigen, T-Cell; 56-45-1/Serine; EC 2.7.11.13/Protein Kinase C

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