PTPN22 activates the PI3K pathway via 14-3-3 tau in T cells

The protein tyrosine phosphatase PTPN22 inhibits T cell activation by dephosphorylating some essential proteins in the T cell receptor-mediated signalling pathway, and its negative regulatory function protects organisms from autoimmune disease. 14-3-3 tau is an adaptor protein that regulates target protein function through its intracellular localization. In the present study, we determined that PTPN22 binds to 14-3-3 tau via the PTPN22-Ser640 phosphorylation side. PTPN22 binding to 14-3-3 tau resulted in 14-3-3 tau-Tyr179 dephosphorylation, and reduced the association between 14-3-3 tau and Shc, which competitively increased 14-3-3 zeta binding to Shc and activated phosphoinositide 3-kinase (PI3K) by bringing it to the membrane. In addition, PTPN22 decreased the tyrosine phosphorylation of p110 to activate PI3K. These two pathways cooperatively affect PI3K activity and the expression of PI3K downstream proteins, such as phosphorylated Akt, mammalian target of rapamycin and forkhead box O1, which inhibited the expression of some proinflammatory factors such as interleukin-1 beta, interleukin-2, interleukin-6, interferon-c and tumour necrosis factor-alpha. Our research provides a preliminary theory for PTPN22 regulating T cell activation, development and immune response via the PI3K/Akt/mammalian target of rapamycin pathway and brings new information for clarifying the functions of PTPN22 in autoimmune diseases.

Automated summary

In this study, it was found that the protein tyrosine phosphatase PTPN22 inhibits T cell activation by dephosphorylating essential proteins in the T cell receptor-mediated signalling pathway. PTPN22 binds to 14-3-3 tau protein and leads to its dephosphorylation, affecting the activity of the PI3K pathway and the expression of inflammatory factors.