| Autor: |
Namir J. Hassan, A N Barclay, Sarah Hanrahan, Marion H. Brown, Nicholas G. Clarkson, M Bomb, Stephen J. Simmonds, M J Puklavec |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Molecular and cellular biology. 39(7) |
| 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 [KD] = 0.5 μM at 37°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: |
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