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Functional requirement of tyrosine residue 429 within CD5 cytoplasmic domain for regulation of T cell activation and survival.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2015 Oct 23; Vol. 466 (3), pp. 381-7. Date of Electronic Publication: 2015 Sep 09. - Publication Year :
- 2015
-
Abstract
- CD5 has been mainly described as a negative regulator of TCR and BCR signaling and recent evidence has shown an important role for this receptor in delivering pro-survival signals. However, the molecular mechanisms underlying these processes remain unresolved. TCR crosslinking leads to phosphorylation of three tyrosine residues within the cytoplasmic tail of CD5 (Y429, Y441 and Y463) leading to the recruitment of signaling molecules like PI3K, c-Cbl and RasGAP; nevertheless, the role of these residues in T cell survival has not yet been assessed. In this study, we show that alanine-scanning mutagenesis of such tyrosine residues, either singly or in combination, leads to an increased thymocyte cell death with or without α-CD3 stimulation. Remarkably, the T-cell death observed with each individual tyrosine mutant was Caspase 3-independent. Furthermore, Y429 mutation resulted in a hyper-phosphorylation of ERK suggesting that this tyrosine residue regulates cell survival through down modulation of TCR signaling. Mutation of Y441 or Y463 did not induce hyper-responsiveness to TCR activation, indicating that they promoted T-cell survival by a TCR signal-independent pathway. Our results show that three tyrosine-based domains within CD5 cytoplasmic tail promote T-cell survival through non-overlapping mechanisms. This study also reveals that Y429 domain of CD5, previously described as a "pseudo ITAM", is functionally an ITIM domain in T cells.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Amino Acid Motifs
Amino Acid Sequence
Animals
Annexin A5 chemistry
Caspase 3 metabolism
Cell Survival
Humans
Mice
Molecular Sequence Data
Phosphorylation
Protein Structure, Tertiary
Receptors, Antigen, T-Cell metabolism
Signal Transduction
T-Lymphocytes cytology
Thymocytes cytology
CD5 Antigens chemistry
Cytoplasm metabolism
Gene Expression Regulation
Lymphocyte Activation
Mutation
Tyrosine chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 466
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 26363459
- Full Text :
- https://doi.org/10.1016/j.bbrc.2015.09.033