Signal transduction by CD28 costimulatory receptor on T cells. B7-1 and B7-2 regulation of tyrosine kinase adaptor molecules.
This study compares the biochemical responses in T cells activated with the CD28 ligands B7-1 and B7-2. The patterns of tyrosine phosphorylation induced in T cells by these two CD28 ligands are identical, but clearly different from the tyrosine phosphorylation induced by the T cell receptor (TCR). The TCR regulates protein complexes mediated by the adapter Grb2 both in vivo and in vitro. In contrast, there is no apparent regulation of in vivo Grb2 complexes in response to B7-1 or B7-2. Rather, B7-1 and B7-2 both induce tyrosine phosphorylation of a different adaptor protein, p62. The regulation of p62 is a unique CD28 response that is not shared with the TCR. These data indicate that B7-1 and B7-2 induce identical tyrosine kinase signal transduction pathways. The data show also that the TCR and CD28 couple to different adapter proteins, which could explain the divergence of TCR and CD28 signal transduction pathways during T cell activation.
Nunès
J A
JA
Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, London, United Kingdom.
Truneh
A
A
Olive
D
D
Cantrell
D A
DA
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000302:isolation & purification / Q000502:physiology*; D018122:B7-1 Antigen / Q000302:isolation & purification / Q000502:physiology*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000302:isolation & purification / Q000502:physiology*; D002460:Cell Line; D002846:Chromatography, Affinity; D066246:ErbB Receptors / Q000378:metabolism; D051380:GRB2 Adaptor Protein; D006801:Humans; D007739:L Cells; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000302:isolation & purification / Q000502:physiology*; D051379:Mice; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; C497965:Cd86 protein, mouse; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C495949:Grb2 protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D011506:Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases