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CARD11 mediates factor-specific activation of NF-κB by the T cell receptor complex

Pomerantz, Joel L. and Denny, Elissa M. and Baltimore, David (2002) CARD11 mediates factor-specific activation of NF-κB by the T cell receptor complex. EMBO Journal, 21 (19). pp. 5184-5194. ISSN 0261-4189. PMCID PMC129028. doi:10.1093/emboj/cdf505.

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NF‐κB is a critical target of signaling downstream of the T cell receptor (TCR) complex, but how TCR signaling activates NF‐κB is poorly understood. We have developed an expression cloning strategy that can identify catalytic and noncatalytic molecules that participate in different pathways of NF‐κB activation. Screening of a mouse thymus cDNA library yielded CARD11, a membrane‐associated guanylate kinase (MAGUK) family member containing CARD, PDZ, SH3 and GUK domains. Using a CARD‐deleted variant of CARD11 and RNA interference (RNAi), we demonstrate that CARD11 mediates NF‐κB activation by αCD3/αCD28 cross‐linking and PMA/ionomycin treatment, but not by TNFα or dsRNA. CARD11 is not required for TCR‐mediated induction of NFAT or AP‐1. CARD11 functions upstream of the IκB‐kinase (IKK) complex and cooperates with Bcl10 in a CARD domain‐dependent manner. RNAi‐rescue experiments suggest that the CARD, coiled‐coil, SH3 and GUK domains of CARD11 are critical for its signaling function. These results implicate CARD11 in factor‐ specific activation of NF‐κB by the TCR complex and establish a role for a MAGUK family member in antigen receptor signaling.

Item Type:Article
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URLURL TypeDescription CentralArticle
Baltimore, David0000-0001-8723-8190
Additional Information:© 2002 European Molecular Biology Organization. Received: 28 May 2002; Accepted: 5 August 2002; Published: 1 October 2002. We thank members of the Baltimore laboratory for helpful discussions and support, G.Nuñez for pc‐FL‐CIPER and J.Alberola‐Ila, M.Boldin, L.Gammill, J.Kim, M.Laurent, M.Meffert, P.Sternberg and T.‐M.Yi for critical reading of the manuscript. During the course of this work, J.L.P. was supported by a postdoctoral fellowship from the Helen Hay Whitney Foundation and is currently a Special Fellow of the Leukemia and Lymphoma Society. This work was supported by NIH grant AI42549‐04.
Funding AgencyGrant Number
Helen Hay Whitney FoundationUNSPECIFIED
Leukemia and Lymphoma SocietyUNSPECIFIED
Subject Keywords:CARD11; expression cloning; MAGUK; NF‐κB; RNAi
Issue or Number:19
PubMed Central ID:PMC129028
Record Number:CaltechAUTHORS:20200506-080808066
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Official Citation:Pomerantz, J.L., Denny, E.M. and Baltimore, D. (2002), CARD11 mediates factor‐specific activation of NF‐κB by the T cell receptor complex. The EMBO Journal, 21: 5184-5194. doi:10.1093/emboj/cdf505
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103017
Deposited By: Tony Diaz
Deposited On:06 May 2020 15:57
Last Modified:16 Nov 2021 18:17

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