G alpha16 protein expression is up- and down-regulated following T-cell activation: disruption of this regulation impairs activation-induced cell responses.
The role of heterotrimeric G proteins in T-cell activation is poorly understood. Here we show that in normal, mature human T-cells, expression of G alpha16, the 43 kDa alpha subunit of G16, varies widely, depending on T-cell activation status. Quiescent blood lymphocytes strongly up-regulate G alpha16 after Leuco A stimulation: protein expression of G alpha16 is maximal at day 4, then decreases. Consistently, in human T-cell clones, expression of G alpha16 is high in the first week following activation and decreases rapidly within the second week. In addition, permanent disruption of regulated G alpha16 expression in Jurkat T-cells by stable overexpression of 43 kDa G alpha16 inhibited Leuco A-induced interleukin-2 production, CD69 up-regulation and cell apoptosis (by 58%, 46% and 74%, respectively), suggesting that coordinate regulation of G alpha16 expression is necessary for optimal activation-induced T-cell responses, and that G alpha16 proteins may be involved in the negative regulation of TCR signalling.
Lippert
E
E
INSERM U463, Groupe Récepteurs et Cytokines, Institut de Biologie, Nantes, France.
Baltensperger
K
K
Jacques
Y
Y
Hermouet
S
S
D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D017209:Apoptosis; D002478:Cells, Cultured; D002999:Clone Cells; D019204:GTP-Binding Proteins / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D019169:Jurkat Cells; D007700:Kinetics; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008970:Molecular Weight; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D013997:Time Factors; D014162:Transfection; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D019204:GTP-Binding Proteins; D007376:Interleukin-2; D037181:Lectins, C-Type; D000099192:CD69 Antigens