T-cell protein tyrosine phosphatase: A role in inflammation and autoimmunity

Substrates targeted by T-cell protein tyrosine phosphatase (TC-PTP). TC-PTP negatively regulates JAK/STAT signaling that leads to the induction of the inflammatory reaction. TC-PTP downregulates signaling mediated by proinflammatory cytokines (IFN-γ, TNF-α, and IL-2) through the dephosphorylation of JAK1, JAK3 and Src kinases, which activate downstream signaling pathways induced by binding of the cytokines to their receptors. As a part of the complex with Importin-β (Imp-β), TC-PTP is able to shuttle from the cytoplasm to the nucleus, where the enzyme can dephosphorylate STATs, the molecules involved in signal transduction and activation of the transcription of a number of genes.

Structure of the protein tyrosine phosphatase, non-receptor 2 (PTPN2) gene encoding T-cell protein tyrosine phosphatase. The PTPN2 gene encompasses nearly 100kb on chromosome 18p11 and includes 10 exons. The location of two SNPs associated with type 1 diabetes is shown.