[PDF][PDF] Mechanism of recruitment of WASP to the immunological synapse and of its activation following TCR ligation
Y Sasahara, R Rachid, MJ Byrne, MA de la Fuente… - Molecular cell, 2002 - cell.com
Molecular cell, 2002•cell.com
F-actin polymerization following engagement of the T cell receptor (TCR) is dependent on
WASP and is critical for T cell activation. The link between TCR and WASP is not fully
understood. In resting cells, WASP exists in a complex with WIP, which inhibits its activation
by Cdc42. We show that the adaptor protein CrkL binds directly to WIP. Further, TCR ligation
results in the formation of a ZAP-70-CrkL-WIP-WASP complex, which is recruited to lipid rafts
and the immunological synapse. TCR engagement also causes PKCθ-dependent …
WASP and is critical for T cell activation. The link between TCR and WASP is not fully
understood. In resting cells, WASP exists in a complex with WIP, which inhibits its activation
by Cdc42. We show that the adaptor protein CrkL binds directly to WIP. Further, TCR ligation
results in the formation of a ZAP-70-CrkL-WIP-WASP complex, which is recruited to lipid rafts
and the immunological synapse. TCR engagement also causes PKCθ-dependent …
Abstract
F-actin polymerization following engagement of the T cell receptor (TCR) is dependent on WASP and is critical for T cell activation. The link between TCR and WASP is not fully understood. In resting cells, WASP exists in a complex with WIP, which inhibits its activation by Cdc42. We show that the adaptor protein CrkL binds directly to WIP. Further, TCR ligation results in the formation of a ZAP-70-CrkL-WIP-WASP complex, which is recruited to lipid rafts and the immunological synapse. TCR engagement also causes PKCθ-dependent phosphorylation of WIP, causing the disengagement of WASP from the WIP-WASP complex, thereby releasing it from WIP inhibition. These results suggest that the ZAP-70-CrkL-WIP pathway and PKCθ link TCR to WASP activation.
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