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Titolo:
REGULATION AND FUNCTION OF THE CD3-GAMMA DXXXLL MOTIF - A BINDING-SITE FOR ADAPTER PROTEIN-1 AND ADAPTER PROTEIN-2 IN-VITRO
Autore:
DIETRICH J; KASTRUP J; NIELSEN BL; ODUM N; GEISLER C;
Indirizzi:
UNIV COPENHAGEN,PANUM INST,INST MED MICROBIOL & IMMUNOL,BLDG 183,BLEGDAMSVEJ 3C DK-2200 COPENHAGEN DENMARK UNIV COPENHAGEN,PANUM INST,INST MED MICROBIOL & IMMUNOL DK-2200 COPENHAGEN DENMARK
Titolo Testata:
The Journal of cell biology
fascicolo: 2, volume: 138, anno: 1997,
pagine: 271 - 281
SICI:
0021-9525(1997)138:2<271:RAFOTC>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL ANTIGEN RECEPTOR; DI-LEUCINE MOTIF; GROWTH-FACTOR RECEPTORS; COATED PIT ADAPTINS; FACTOR-II RECEPTOR; CYTOPLASMIC TAIL; INVARIANT CHAIN; ENDOCYTIC PATHWAY; T3-GAMMA SUBUNIT; INVITRO BINDING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
55
Recensione:
Indirizzi per estratti:
Citazione:
J. Dietrich et al., "REGULATION AND FUNCTION OF THE CD3-GAMMA DXXXLL MOTIF - A BINDING-SITE FOR ADAPTER PROTEIN-1 AND ADAPTER PROTEIN-2 IN-VITRO", The Journal of cell biology, 138(2), 1997, pp. 271-281

Abstract

Several receptors are downregulated by internalization after ligand binding. Regulation of T cell receptor (TCR) expression is an importantstep in T cell activation, desensitization, and tolerance induction, One way T cells regulate TCR expression is by phosphorylation/dephosphorylation of the TCR subunit clusters of differentiation (CD)3 gamma. Thus, phosphorylation of CD3 gamma serine 126 (S126) causes a downregulation of the TCR. In this study, we have analyzed the CD3 gamma internalization motif in three different systems in parallel: in the context of the complete multimeric TCR; in monomeric CD4/CD3 gamma chimeras;and in vitro by binding CD3 gamma peptides to clathrin-coated vesicleadaptor proteins (APs), We find that the CD3 gamma D(127)xxxLL(131/132) sequence represents one united motif for binding of both AP-1 and AP-2, and that this motif functions as an active sorting motif in monomeric CD4/CD3 gamma molecules independently of S126. An acidic amino acid is required at position 127 and a leucine (L) is required at position 131, whereas the requirements for position 132 are more relaxed, The spacing between aspartic acid 127 (D127) and L131 is crucial for thefunction of the motif in vivo and for AP binding in vitro. Furthermore, we provide evidence indicating that phosphorylation of CD3 gamma S126 in the context of the complete TCR induces a conformational change that exposes the DxxxLL sequence for AP binding, Exposure of the DxxxLL motif causes an increase in the TCR internalization rate and we demonstrate that this leads to an impairment of TCR signaling, On the basis of the present results, we propose the existence of at least three different types of L-based receptor sorting motifs.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 09:17:27