Intensity and duration of TCR signaling is limited by p38 phosphorylation of ZAP-70T293 and destabilization of the signalosome.
Proc Natl Acad Sci U S A
; 115(9): 2174-2179, 2018 02 27.
Article
en En
| MEDLINE
| ID: mdl-29440413
ABSTRACT
ZAP-70 is a tyrosine kinase that is essential for initiation of T cell antigen receptor (TCR) signaling. We have found that T cell p38 MAP kinase (MAPK), which is directly phosphorylated and activated by ZAP-70 downstream of the TCR, in turn phosphorylates Thr-293 in the interdomain B region of ZAP-70. Mutant T cells expressing ZAP-70 with an alanine substitution at this residue (ZAP-70T293A) had enhanced TCR proximal signaling and increased effector responses. Lack of ZAP-70T293 phosphorylation increased association of ZAP-70 with the TCR and prolonged the existence of TCR signaling microclusters. These results identify a tight negative feedback loop in which ZAP-70-activated p38 reciprocally phosphorylates ZAP-70 and destabilizes the signaling complex.
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Texto completo:
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Banco de datos:
MEDLINE
Asunto principal:
Genes Codificadores de los Receptores de Linfocitos T
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Proteínas Quinasas p38 Activadas por Mitógenos
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Proteína Tirosina Quinasa ZAP-70
Límite:
Humans
Idioma:
En
Año:
2018
Tipo del documento:
Article