Mechanism of recruitment of WASP to the immunological synapse and of its activation following TCR ligation |
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Authors: | Sasahara Yoji Rachid Rima Byrne Michael J de la Fuente Miguel A Abraham Robert T Ramesh Narayanaswamy Geha Raif S |
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Institution: | Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. |
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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 PKCtheta-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 PKCtheta link TCR to WASP activation. |
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