Figure 1

(A) The role of PKC in TCR-CD28-induced signaling in T cells. In response to TCR-CD28 stimulation, PKC is recruited and activated, which enables activation of JNK and NF-κB. The PKC-mediated activation of NFAT is controversial. Taken together, PKC plays the central role in the TCR-CD28-mediated induction of gene transcription, leading to proliferation and cytokine secretion in T cells. (B) The IL-2R consists of three subunits: α-chain (IL-2R; i.e., CD25), β-chain (IL-2Rß; CD122) and the common cytokine-receptor γ-chain (γc; CD132). Binding of IL-2 to the heterotrimer IL-2R initiates the activation of Janus-activated kinase 3 (JAK3), which associates with the γc, while JAK1 associates with IL-2Rβ. Both phosphorylate tyrosine residues in the cytoplasmic part of IL-2Rβ and the γc. Subsequently, the JAK molecules are activated, which amplifies the association of these tyrosine kinases and the signal transducer and activator of transcription 5 (STAT5) or STAT3 with the cytoplasmic tail of IL-2Rβ. Recruited STATs are phosphorylated by activated JAKs. Activated STATs translocate to the nucleus and activate gene transcription of interferons, e.g., (IFN)-γ, granzyme B, Fasligand (FasL), suppressors of cytokine signaling (SOCS) and the transcription factor for regulatory T cells: FOXP3 binding to DNA promoter sequences.