THEMIS increases TCR signaling in CD4⁺CD8⁺ thymocytes by inhibiting the activity of the tyrosine phosphatase SHP1.

ABSTRACT: The T cell lineage-restricted protein THEMIS plays a critical role in T cell development at the positive selection stage. In the SHP1 activation model, THEMIS is proposed to enhance the activity of the tyrosine phosphatase SHP1 (encoded by Ptpn6), thereby dampening T cell antigen receptor (TCR) signaling and preventing the inappropriate negative selection of CD4⁺CD8⁺ thymocytes by positively selecting ligands. In contrast, in the SHP1 inhibition model, THEMIS is proposed to suppress SHP1 activity, rendering CD4⁺CD8⁺ thymocytes more sensitive to TCR signaling initiated by low-affinity ligands to promote positive selection. We sought to resolve the controversy regarding the molecular function of THEMIS. We found that the defect in positive s

SUBMITTER: Choi S 

PROVIDER: S-EPMC10410529 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature