Noncanonical mode of ERK action controls alternative αß and γδ T cell lineage fates.
Immunity
; 41(6): 934-46, 2014 Dec 18.
Article
em En
| MEDLINE
| ID: mdl-25526308
Gradations in extracellular regulated kinase (ERK) signaling have been implicated in essentially every developmental checkpoint or differentiation process encountered by lymphocytes. Yet, despite intensive effort, the molecular basis by which differences in ERK activation specify alternative cell fates remains poorly understood. We report here that differential ERK signaling controls lymphoid-fate specification through an alternative mode of action. While ERK phosphorylates most substrates, such as RSK, by targeting them through its D-domain, this well-studied mode of ERK action was dispensable for development of γδ T cells. Instead, development of γδ T cells was dependent upon an alternative mode of action mediated by the DEF-binding pocket (DBP) of ERK. This domain enabled ERK to bind a distinct and select set of proteins required for specification of the γδ fate. These data provide the first in vivo demonstration for the role of DBP-mediated interactions in orchestrating alternate ERK-dependent developmental outcomes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Receptores de Antígenos de Linfócitos T gama-delta
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Receptores de Antígenos de Linfócitos T alfa-beta
/
MAP Quinases Reguladas por Sinal Extracelular
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article