Phosphorylation of CrkL S114 induced by common gamma chain cytokines and T-cell receptor signal transduction.
Sci Rep
; 11(1): 16951, 2021 08 20.
Article
en En
| MEDLINE
| ID: mdl-34417497
T-cell activation and cellular expansion by common gamma chain cytokines such as Interleukin-2 is necessary for adaptive immunity. However, when unregulated these same pathways promote pathologies ranging from autoimmune disorders to cancer. While the functional role of Interleukin-2 and downstream effector molecules is relatively clear, the repertoire of phosphoregulatory proteins downstream of this pathway is incomplete. To identify phosphoproteins downstream of common gamma chain receptor, YT cells were radiolabeled with [32P]-orthophosphate and stimulated with Interleukin-2. Subsequently, tyrosine phosphorylated proteins were immunopurified and subjected to tandem mass spectrometry-leading to the identification of CrkL. Phosphoamino acid analysis revealed concurrent serine phosphorylation of CrkL and was later identified as S114 by mass spectrometry analysis. S114 was inducible through stimulation with Interleukin-2 or T-cell receptor stimulation. Polyclonal antibodies were generated against CrkL phospho-S114, and used to show its inducibility by multiple stimuli. These findings confirm CrkL as an Interleukin-2 responsive protein that becomes phosphorylated at S114 by a kinase/s downstream of PI3K and MEK/ERK signaling.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fosfoserina
/
Receptores de Antígenos de Linfocitos T
/
Transducción de Señal
/
Citocinas
/
Interleucina-2
/
Proteínas Adaptadoras Transductoras de Señales
/
Subunidad gamma Común de Receptores de Interleucina
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Sci Rep
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido