PTPN22 phosphorylation acts as a molecular rheostat for the inhibition of TCR signaling.

ABSTRACT: The hematopoietic-specific protein tyrosine phosphatase nonreceptor type 22 (PTPN22) is encoded by a major autoimmunity risk gene. PTPN22 inhibits T cell activation by dephosphorylating substrates involved in proximal T cell receptor (TCR) signaling. Here, we found by mass spectrometry that PTPN22 was phosphorylated at Ser⁷⁵¹ by PKCα in Jurkat and primary human T cells activated with phorbol ester/ionomycin or antibodies against CD3/CD28. The phosphorylation of PTPN22 at Ser⁷⁵¹ prolonged its half-life by inhibiting K48-linked ubiquitination and impairing recruitment of the phosphatase to the plasma membrane, which is necessary to inhibit proximal TCR signaling. Additionally, the phosphorylation of PTPN22 at Ser⁷⁵¹ enhanced the interaction of PTPN22 with the

SUBMITTER: Yang S 

PROVIDER: S-EPMC7263369 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature