CD6 Regulates T-Cell Responses through Activation-Dependent Recruitment of the Positive Regulator SLP-76
| Autor: | Nicholas G. Clarkson, Namir J. Hassan, M J Puklavec, Marion H. Brown, Sarah Hanrahan, A. Neil Barclay, Martine Bomb, Stephen J. Simmonds |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Antigens
Differentiation T-Lymphocyte Interleukin 2 T-Lymphocytes T cell Regulator Plasma protein binding Biology CD5 Antigens Lymphocyte Activation Jurkat cells src Homology Domains Jurkat Cells Mice Antigens CD Activated-Leukocyte Cell Adhesion Molecule medicine Animals Humans Phosphorylation Author Correction Molecular Biology Adaptor Proteins Signal Transducing Antibodies Monoclonal Signal transducing adaptor protein Cell Biology Phosphoproteins Ligand (biochemistry) Phosphorylated Peptide Cell biology medicine.anatomical_structure Interleukin-2 Peptides Author's Corrections Protein Binding medicine.drug |
| Zdroj: | Molecular and Cellular Biology. 29:3452-3452 |
| ISSN: | 1098-5549 |
| Popis: | Deciphering the role of lymphocyte membrane proteins depends on dissecting the role of a protein in the steady state and on engagement with its ligand. We show that expression of CD6 in T cells limits their responsiveness but that engagement by the physiological ligand CD166 gives costimulation. This costimulatory effect of CD6 is mediated through phosphorylation-dependent binding of a specific tyrosine residue, 662Y, in its cytoplasmic region to the adaptor SLP-76. A direct interaction between SLP-76 and CD6 was shown by binding both to a phosphorylated peptide (equilibrium dissociation constant [K(D)] = 0.5 muM at 37 degrees C) and, using a novel approach, to native phosphorylated CD6. Evidence that CD6 and SLP-76 interact in cells was obtained in coprecipitation experiments with normal human T cells. Analysis of human CD6 mutants in a murine T-cell hybridoma model showed that both costimulation by CD6 and the interaction between CD6 and SLP-76 were dependent on 662Y. The results have implications for regulation by CD6 and the related T-cell surface protein, CD5. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|