In:
European Journal of Immunology, Wiley, Vol. 38, No. 11 ( 2008-11), p. 3208-3218
Abstract:
Here, we examined the functional involvement of heterotrimeric G‐proteins in TCR‐induced immune responses. TCR/CD3 crosslinking resulted in activation of both Gαq and Gαs, but not Gαi‐2. Targeting of Gαs, Gαi‐2 and Gαq using siRNA demonstrated a specific role of Gαq in TCR signaling. Jurkat TAg T cells with Gαq knockdown displayed reduced activation of Lck and LAT phosphorylation, but paradoxically showed sustained ERK1/2 phosphorylation and increased NFAT‐AP‐1‐reporter activity implicating Gαq in the negative control of downstream signaling and IL‐2‐promoter activity. Primary T cells isolated from Gαq‐deficient mice had a similar TCR signaling response with reduced proximal LAT phosphorylation, sustained ERK1/2 phosphorylation and augmented immune responses including increased secretion of IL‐2, IL‐5, IL‐12 and TNF‐α. The effects on NFAT‐AP‐1‐reporter activity were sensitive to the Src family kinase inhibitor PP2 and were reversed by transient expression of constitutively active Lck. Furthermore, expression of constitutively active Gαq Q209L elevated Lck activity and Zap‐70 phosphorylation. Together these data argue for a role of Gαq in the fine‐tuning of proximal TCR signals at the level of Lck and a negative regulatory role of Gαq in transcriptional activation of cytokine responses.
Type of Medium:
Online Resource
ISSN:
0014-2980
,
1521-4141
DOI:
10.1002/eji.200838195
Language:
English
Publisher:
Wiley
Publication Date:
2008
detail.hit.zdb_id:
1491907-2
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