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

Joel L Pomerantz, Elissa M. Denny, David Baltimore

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5184-5194
Number of pages11
JournalThe EMBO journal
Volume21
Issue number19
DOIs
StatePublished - Oct 1 2002
Externally publishedYes

Fingerprint

T-Cell Antigen Receptor
Chemical activation
Guanylate Kinases
src Homology Domains
RNA Interference
RNA
Thymus
Antigen Receptors
Ionomycin
Cloning
Transcription Factor AP-1
Gene Library
Thymus Gland
Organism Cloning
Screening
Phosphotransferases
Molecules
Experiments
Therapeutics

Keywords

  • CARD11
  • Expression cloning
  • MAGUK
  • NF-κB
  • RNAi

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

CARD11 mediates factor-specific activation of NF-κB by the T cell receptor complex. / Pomerantz, Joel L; Denny, Elissa M.; Baltimore, David.

In: The EMBO journal, Vol. 21, No. 19, 01.10.2002, p. 5184-5194.

Research output: Contribution to journalArticle

Pomerantz, Joel L ; Denny, Elissa M. ; Baltimore, David. / CARD11 mediates factor-specific activation of NF-κB by the T cell receptor complex. In: The EMBO journal. 2002 ; Vol. 21, No. 19. pp. 5184-5194.
@article{75c9c0b419834d09813b36cdb87e361d,
title = "CARD11 mediates factor-specific activation of NF-κB by the T cell receptor complex",
abstract = "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.",
keywords = "CARD11, Expression cloning, MAGUK, NF-κB, RNAi",
author = "Pomerantz, {Joel L} and Denny, {Elissa M.} and David Baltimore",
year = "2002",
month = "10",
day = "1",
doi = "10.1093/emboj/cdf505",
language = "English (US)",
volume = "21",
pages = "5184--5194",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "19",

}

TY - JOUR

T1 - CARD11 mediates factor-specific activation of NF-κB by the T cell receptor complex

AU - Pomerantz, Joel L

AU - Denny, Elissa M.

AU - Baltimore, David

PY - 2002/10/1

Y1 - 2002/10/1

N2 - 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.

AB - 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.

KW - CARD11

KW - Expression cloning

KW - MAGUK

KW - NF-κB

KW - RNAi

UR - http://www.scopus.com/inward/record.url?scp=0036790507&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036790507&partnerID=8YFLogxK

U2 - 10.1093/emboj/cdf505

DO - 10.1093/emboj/cdf505

M3 - Article

VL - 21

SP - 5184

EP - 5194

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 19

ER -