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© Institut Pasteur
Macrophage apparaissant derrière un lymphocyte. Image colorisée.
Publication : Immunity

Induction of the NF-kappaB cascade by recruitment of the scaffold molecule NEMO to the T cell receptor

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Immunity - 01 Jan 2003

Weil R, Schwamborn K, Alcover A, Bessia C, Di Bartolo V, Israël A

Link to Pubmed [PMID] – 12530972

Immunity 2003 Jan;18(1):13-26

The mechanism by which TCR signaling activates NF-kappaB is poorly understood. We demonstrate here that the IKK kinase complex is recruited to the immunological synapse and can be coprecipitated with the TCR after T cell activation. Using ZAP-70-deficient T cells expressing a hybrid molecule between the SH2 domain of ZAP-70 and NEMO/IKKgamma, we showed that targeting NEMO to the immunological synapse, and more specifically its 120 N-terminal amino acids, was sufficient to selectively restore NF-kappaB activation in response to TCR ligation. Finally, we demonstrated that targeting of NEMO to the membrane of T cells was sufficient to induce constitutive NF-kappaB activation. This study shows that the localization of NEMO to the immunological synapse is important for TCR-induced NF-kappaB activation and offers a powerful system to dissect the NF-kappaB cascade in T cells.

https://www.ncbi.nlm.nih.gov/pubmed/12530972