Figure 3: Activation of protein tyrosine phosphatases (PTP) and regulation of TCR signalling
TCR triggering activates a number of signalling pathways that include calcium, MAPK and NFΚB. Co-inhibitory receptors recruit SH2-domain containing protein tyrosine phosphatases, SHP-1 & SHP-1 through binding of the PTP SH2 domains to phosphorylated ITIMs in their cytoplasmic domains. Engagement of PTP SH2 domains leads to activation of the PTPs which dephosphorylate key substrates that lie within the TCR signalling pathways. CTLA-4 and PD-1 are shown as specific examples with the PTPs that are recruited and the substrates that are dephosphorylated. In addition to PTPs, CTLA has been shown to associate with the protein phosphatase PP2A and negatively regulate PI3K. CTLA-4-Cytotoxic T-Lymphocyte Antigen 4, ITIM-immunoreceptor tyrosine-based inhibition motif, ITSMimmunoreceptor tyrosine-based switch motif, PD-1-Programmed cell death protein 1 SHP-1/2-Src homology 2-containing tyrosine phosphatase 1/2, Siglecs-sialic acid binding Ig-like lectins, PP2A–protein phosphatase 2A.