Interaction between G proteins and tyrosine kinases upon T cell receptor.CD3-mediated signaling.
Engagement of the T cell receptor (TCR).CD3 complex results in the induction of multiple intracellular events, with protein tyrosine kinases playing a pivotal role in their initiation. Biochemical studies also exist suggesting the involvement of heterotrimeric GTP-binding proteins (G proteins); however, the functional consequence of this participation in TCR.CD3-mediated signaling is unresolved. Here, we report TCR.CD3-mediated guanine nucleotide exchange among the 42-kDa G protein alpha subunits of the G alpha q/11 family, their physical association with CD3 epsilon, and the G alpha 11-dependent activation of phospholipase C beta. Protein tyrosine kinase inhibitors, however, abrogate TCR.CD3-mediated G protein activation. Quite interesting is the observation that cells transfected with a function-deficient mutant of G alpha 11 display diminished tyrosine phosphorylation of TCR.CD3 zeta and epsilon chains, as well as ZAP-70, upon anti-CD3 antibody triggering. These data indicate the involvement of the G alpha q/11 family in TCR.CD3 signaling at a step proximal to the receptor and suggest a reciprocal regulation between tyrosine kinases and G proteins in T cells.
Department of Biology and Molecular Biology Institute, San Diego State University, California 92182, USA.
J
J
Stanners
P S
PS
Kabouridis
K L
KL
McGuire
C D
CD
Tsoukas
D000911:Antibodies, Monoclonal; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D019833:Genistein; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D014162:Transfection
D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D007529:Isoflavones; D009838:Oligodeoxyribonucleotides; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011994:Recombinant Proteins; D019000:Phosphotyrosine; D015544:Inositol 1,4,5-Trisphosphate; D006160:Guanosine Triphosphate; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins