Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1128/MCB.00688-06

Type

Journal article

Journal

Mol Cell Biol

Publication Date

09/2006

Volume

26

Pages

6727 - 6738

Keywords

Activated-Leukocyte Cell Adhesion Molecule, Adaptor Proteins, Signal Transducing, Animals, Antibodies, Monoclonal, Antigens, CD, Antigens, Differentiation, T-Lymphocyte, CD5 Antigens, Humans, Interleukin-2, Jurkat Cells, Lymphocyte Activation, Mice, Peptides, Phosphoproteins, Phosphorylation, Protein Binding, T-Lymphocytes, src Homology Domains