A novel gain-of-function phosphorylation site modulates PTPN22 inhibition of TCR signaling.

ABSTRACT: Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) is encoded by a major autoimmunity gene and is a known inhibitor of T cell receptor (TCR) signaling and drug target for cancer immunotherapy. However, little is known about PTPN22 posttranslational regulation. Here, we characterize a phosphorylation site at Ser³²⁵ situated C terminal to the catalytic domain of PTPN22 and its roles in altering protein function. In human T cells, Ser³²⁵ is phosphorylated by glycogen synthase kinase-3 (GSK3) following TCR stimulation, which promotes its TCR-inhibitory activity. Signaling through the major TCR-dependent pathway under PTPN22 control was enhanced by CRISPR/Cas9-mediated suppression of Ser³²⁵ phosphorylation and inhibited by mimicking it via glutamic acid s

SUBMITTER: Zhuang C 

PROVIDER: S-EPMC11237943 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature