Recruitment of calcineurin to the TCR positively regulates T cell activation.

ABSTRACT: Calcineurin is a phosphatase whose primary targets in T cells are NFAT transcription factors, and inhibition of calcineurin activity by treatment with cyclosporin A (CsA) or FK506 is a cornerstone of immunosuppressive therapies. Here we found that calcineurin was recruited to the T cell antigen receptor (TCR) signaling complex, where it reversed inhibitory phosphorylation of the tyrosine kinase Lck on Ser59 (Lck^S59). Loss of calcineurin activity impaired phosphorylation of Tyr493 of the tyrosine kinase ZAP-70 (ZAP-70^Y493), as well as some downstream pathways in a manner consistent with signaling in cells expressing Lck^S59A (Lck that cannot be phosphorylated) or Lck^S59E (a phosphomimetic mutant). Notably, CsA inhibited integrin-LFA-1-dependent and

SUBMITTER: Dutta D 

PROVIDER: S-EPMC6352896 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature