G-ALPHA(16) PROTEIN EXPRESSION IS UP-REGULATED 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 u nderstood, Here we show that in normal, mature human T-cells, expressi on of G alpha(16), the 43 kDa alpha subunit of G(16), varies widely, d epending on T-cell activation status, Quiescent blood lymphocytes stro ngly up-regulate G alpha(16) after Leuco A stimulation: protein expres sion of G alpha(16) is maximal at day 4, then decreases, Consistently, in human T-cen clones, expression of G alpha(16), is high in the firs t week following activation and decreases rapidly within the second we ek. In addition, permanent disruption of regulated G alpha(16) express ion in Jurkat T-cells by stable overexpression of 43 kDa G alpha(16), inhibited Leuco A-induced interleukin-2 production, CD69 up-regulation and cell apoptosis (by 58%, 46% and 74%, respectively), suggesting th at coordinate regulation of G alpha(16) expression is necessary far op timal activation-induced T-cell responses, and that G alpha(16) protei ns may be involved in the negative regulation of TCR signalling. (C) 1 997 Federation of European Biochemical Societies.