Filamin A Is Required for T Cell Activation Mediated by Protein Kinase C-θ

摘要: Induction of T cell responses following engagement the Ag-specific TCR depends on TCR-initiated rearrangements cellular actin cytoskeleton and highly coordinated tightly regulated interactions diverse intracellular signaling proteins. In this study, we show that filamin A (FLNa), an actin-binding signal mediator scaffolding protein, is required for activation. Following Ag stimulation, FLNa was recruited to cell-APC contact area, where it colocalized with protein kinase C-θ (PKCθ). Depletion by RNA interference did not affect TCR-induced early tyrosine phosphorylation or polymerization but, nevertheless, resulted in impaired IL-2 expression human primary cells reduced activation NF-κB , AP-1 NFAT reporter genes transfected cells. stimulation induced stable physical association PKCθ. Furthermore, TCR/CD28-induced membrane translocation PKCθ inhibited FLNa-depleted These results reveal novel role TCR/CD28 pathway leading transcription factor production, suggest mediated, part, through inducible interaction