Interaction between G proteins and tyrosine kinases upon T cell receptor.CD3-mediated signaling.
J Biol Chem
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.
|Title:||Interaction between G proteins and tyrosine kinases upon T cell receptor.CD3-mediated signaling.|
|Open access status:||An open access publication|
|Keywords:||Antibodies, Monoclonal, Base Sequence, Blotting, Western, Cell Line, Cell Membrane, Enzyme Inhibitors, GTP-Binding Proteins, Genistein, Guanosine Triphosphate, Humans, Inositol 1,4,5-Trisphosphate, Isoflavones, Kinetics, Molecular Sequence Data, Mutagenesis, Site-Directed, Oligodeoxyribonucleotides, Phosphorylation, Phosphotyrosine, Protein-Tyrosine Kinases, Receptor-CD3 Complex, Antigen, T-Cell, Recombinant Proteins, Signal Transduction, T-Lymphocytes, Transfection|
|UCL classification:||UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences
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