TY - JOUR
T1 - Mechanism of recruitment of WASP to the immunological synapse and of its activation following TCR ligation
AU - Sasahara, Yoji
AU - Rachid, Rima
AU - Byrne, Michael J.
AU - De la Fuente, Miguel A.
AU - Abraham, Robert T.
AU - Ramesh, Narayanaswamy
AU - Geha, Raif S.
N1 - Funding Information:
The authors thank N. Martinez-Quiles, I. Anton, J. Orange, and V. Heissmeyer for help, B. Mayer for the Crk cDNAs, A. Weiss for J14 cells, Dan R. Littman for PKCθ knockout mice, and F. Alt for critical reading of the manuscript. This work was supported by USPHS grant HL-59561, the March of Dimes, Model Foundation, and Baxter Corporation.
PY - 2002/12/1
Y1 - 2002/12/1
N2 - 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.
AB - 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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U2 - 10.1016/S1097-2765(02)00728-1
DO - 10.1016/S1097-2765(02)00728-1
M3 - Article
C2 - 12504004
AN - SCOPUS:0036928182
SN - 1097-2765
VL - 10
SP - 1269
EP - 1281
JO - Molecular Cell
JF - Molecular Cell
IS - 6
ER -