CCR7-mediated LFA-1 functions in T cells are regulated by 2 independent ADAP/SKAP55 modules.
Blood
; 119(3): 777-85, 2012 Jan 19.
Article
en En
| MEDLINE
| ID: mdl-22117043
ABSTRACT
The ß2-integrin lymphocyte function-associated antigen-1 (LFA-1) plays a crucial role within the immune system. It regulates the interaction between T cells and antigen-presenting cells and facilitates T-cell adhesion to the endothelium, a process that is important for lymphocyte extravasation and homing. Signals mediated via the T-cell receptor and the chemokine receptor CCR7 activate LFA-1 through processes known as inside-out signaling. The molecular mechanisms underlying inside-out signaling are not completely understood. Here, we have assessed the role of the ADAP/SKAP55 module for CCR7-mediated signaling. We show that loss of the module delays homing and reduces intranodal T-cell motility in vivo. This is probably because of a defect in CCR7-mediated adhesion that affects both affinity and avidity regulation of LFA-1. Further analysis of how the ADAP/SKAP55 module regulates CCR7-induced integrin activation revealed that 2 independent pools of the module are expressed in T cells. One pool interacts with a RAPL/Mst1 complex, whereas the other pool is linked to a RIAM/Mst1/Kindlin-3 complex. Importantly, both the RAPL/Mst1 and the RIAM/Mst1/Kindlin-3 complexes require ADAP/SKAP55 for binding to LFA-1 upon CCR7 stimulation. Hence, 2 independent ADAP/SKAP55 modules are essential components of the signaling machinery that regulates affinity and avidity of LFA-1 in response to CCR7.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fosfoproteínas
/
Linfocitos T
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Regulación de la Expresión Génica
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Antígeno-1 Asociado a Función de Linfocito
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Proteínas Adaptadoras Transductoras de Señales
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Receptores CCR7
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Blood
Año:
2012
Tipo del documento:
Article
País de afiliación:
Alemania