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- W98983546 abstract "The growth arrest and DNA damage-inducible gene 45 (Gadd45) proteins mediate inflammatory cytokine production by regulating kinases upstream of the p38 mitogen-activated protein kinase (MAPK) in T helper type 1 (Th1) and dendritic cells. The phenotype of Gadd45a-deficient mice, which develop lupus-like autoimmunity, led to the description of a p38 activation pathway independent of the p38 upstream MAPK cascade; this pathway is triggered by phosphorylation of the non-canonical p38 residue Tyr323 in response to T cell receptor (TCR) stimulation. Gadd45a is a natural inhibitor of TCR signaling-induced p38 activation in T cells, which acts by binding p38 and blocking Tyr323p38 phosphorylation. In vitro and in vivo studies suggest that the TCR signaling pathway controls the maintenance of central and peripheral tolerance as well as interferon gamma (IFNγ) production in response to TCR activation. The discovery of the TCR signaling pathway and the role of Gadd45a as a T cell-specific inhibitor of p38 allow development of a new class of p38 inhibitors. Selective inhibition of the TCR signaling pathway with small molecule inhibitors that block Tyr323p38 phosphorylation might cause fewer side effects than currently available inhibitors of p38, and could be especially useful for the treatment of human Th1-type autoimmune disease." @default.
- W98983546 created "2016-06-24" @default.
- W98983546 creator A5025379829 @default.
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- W98983546 date "2009-12-28" @default.
- W98983546 modified "2023-09-23" @default.
- W98983546 title "The Role of Gadd45a in Suppression of Autoimmunity" @default.
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