title: T Cell Costimulation by CD6 Is Dependent on Bivalent Binding of a GADS/SLP-76 Complex.
abstract: The cell surface receptor CD6 regulates T cell activation in both activating and inhibitory manners. The adaptor protein SLP-76 is recruited to the phosphorylated CD6 cytoplasmic Y662 residue during T cell activation, providing an activating signal to T cells. In this study, a biochemical approach identified the SH2 domain-containing adaptor protein GADS as the dominant interaction partner for the CD6 cytoplasmic Y629 residue. Functional experiments in human Jurkat and primary T cells showed that both mutations Y629F and Y662F abolished costimulation by CD6. In addition, a restraint on T cell activation by CD6 was revealed in primary T cells expressing CD6 mutated at Y629 and Y662. These data are consistent with a model in which bivalent recruitment of a GADS/SLP-76 complex is required for costimulation by CD6.
authors.affiliation: Sir William Dunn School of Pathology, Oxford, United Kingdom.
authors.forename: Johannes
authors.initials: J
authors.lastname: Breuning
authors.affiliation: Sir William Dunn School of Pathology, Oxford, United Kingdom Marion.Brown@path.ox.ac.uk.
authors.forename: Marion H
authors.initials: MH
authors.lastname: Brown
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D008954:Models, Biological; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology*; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C062279:CD6 antigen; C409587:GRAP2 protein, human; D007376:Interleukin-2; D050505:Mutant Proteins; D010750:Phosphoproteins; C092947:SLP-76 signal Transducing adaptor proteins
keywords: CD6; GADS; SLP-76; T cells; signal transduction