THEMIS enhances TCR signaling and enables positive selection by selective inhibition of the phosphatase SHP-1.
Nat Immunol
; 18(4): 433-441, 2017 04.
Article
en En
| MEDLINE
| ID: mdl-28250424
ABSTRACT
THEMIS, a T cell-specific protein with high expression in CD4+CD8+ thymocytes, has a crucial role in positive selection and T cell development. THEMIS lacks defined catalytic domains but contains two tandem repeats of a distinctive module of unknown function (CABIT). Here we found that THEMIS directly regulated the catalytic activity of the tyrosine phosphatase SHP-1. This action was mediated by the CABIT modules, which bound to the phosphatase domain of SHP-1 and promoted or stabilized oxidation of SHP-1's catalytic cysteine residue, which inhibited the tyrosine-phosphatase activity of SHP-1. Deletion of SHP-1 alleviated the developmental block in Themis-/- thymocytes. Thus, THEMIS facilitates thymocyte positive selection by enhancing the T cell antigen receptor signaling response to low-affinity ligands.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Receptores de Antígenos de Linfocitos T
/
Linfocitos T
/
Transducción de Señal
/
Péptidos y Proteínas de Señalización Intracelular
/
Proteína Tirosina Fosfatasa no Receptora Tipo 6
/
Selección Clonal Mediada por Antígenos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos