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Lipid raft assembly and Lck recruitment in TRAIL costimulation mediates NF-κB activation and T cell proliferation.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2011 Jan 15; Vol. 186 (2), pp. 931-9. Date of Electronic Publication: 2010 Dec 15. - Publication Year :
- 2011
-
Abstract
- The TNF-related apoptosis-inducing ligand was shown to provide a costimulatory signal that cooperates with the TCR/CD3 complex to induce T cell proliferation and cytokine production. Although a number of signaling pathways were linked to the TCR/CD3 complex, it is not known how these two receptors cooperate to induce T cell activation. In this study, we show that TRAIL-induced costimulation of T cells depends on activation of the NF-κB pathway. TRAIL induced the NF-κB pathway by phosphorylation of inhibitor of κB factor kinase and protein kinase C in conjunction with anti-CD3. Furthermore, we demonstrated that TRAIL costimulation induced phosphorylation of the upstream TCR-proximal tyrosine kinases, Lck and ZAP70. Ligation of the TRAIL by its soluble receptor, DR4-Fc, alone was able to induce the phosphorylation of Lck and ZAP70 and to activate the NF-κB pathway; however, it was insufficient to fully activate T cells to support T cell proliferation. In contrast, TRAIL engagement in conjunction with anti-CD3, but not TRAIL ligation alone, induced lipid raft assembly and recruitment of Lck and PKC. These results demonstrate that TRAIL costimulation mediates NF-κB activation and T cell proliferation by lipid raft assembly and recruitment of Lck. Our results suggest that in TRAIL costimulation, lipid raft recruitment of Lck integrates mitogenic NF-κB-dependent signals from the TCR and TRAIL in T lymphocytes.
- Subjects :
- Humans
Jurkat Cells
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) physiology
Membrane Microdomains physiology
NF-kappa B physiology
Protein Transport immunology
Signal Transduction immunology
T-Lymphocytes cytology
T-Lymphocytes metabolism
ZAP-70 Protein-Tyrosine Kinase biosynthesis
ZAP-70 Protein-Tyrosine Kinase physiology
Cell Proliferation
Lymphocyte Activation immunology
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) metabolism
Membrane Microdomains metabolism
NF-kappa B metabolism
T-Lymphocytes immunology
TNF-Related Apoptosis-Inducing Ligand physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 186
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 21160038
- Full Text :
- https://doi.org/10.4049/jimmunol.1001092