Stanners, J; Kabouridis, PS; McGuire, KL; Tsoukas, CD; (1995) Interaction between G proteins and tyrosine kinases upon T cell receptor·CD3-mediated signaling. Journal of Biological Chemistry , 270 (51) 30635 - 30642. 10.1074/jbc.270.51.30635.
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 a subunits of the Gαq/11 family, their physical association with CD3 ε, and the Gα11- dependent activation of phospholipase C β. 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 Gα11 display diminished tyrosine phosphorylation of TCR·CD3 ζ and ε chains, as well as ZAP-70, upon anti-CD3 antibody triggering. These data indicate the involvement of the Gαq/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|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)|
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