Figure 6
The calcium/calcineurin/NFAT signalling pathway in T cells. After TCR ligation and PLCγ1 activation, newly synthesized IP3 binds to tetrameric IP3 receptor complexes inducing the release of intracellular calcium stores from the sarco-endoplasmic reticulum. Store depletion leads directly to the opening of ICRAC or store-operated channels (SOC) in the plasma membrane through mechanisms that are unclear. This leads ultimately to activation of the serine phosphatase calcineurin, dephosphorylation of NFAT, and translocation of this transcription factor to the nucleus. For many genes, NFAT binds cooperatively to AP-1 complexes for optimal gene transcription. AP, activator protein; CsA, cyclosporin A; iCa2+, intracellular calcium; ICRAC, calcium-release-activated calcium current; IP, inositol phosphate; P, phosphate group; PLCγ, phospholipase Cγ; TCR, T-cell receptor.