| First Author | Grabiner BC | Year | 2007 |
| Journal | Genes Dev | Volume | 21 |
| Issue | 8 | Pages | 984-96 |
| PubMed ID | 17438001 | Mgi Jnum | J:121114 |
| Mgi Id | MGI:3709252 | Doi | 10.1101/gad.1502507 |
| Citation | Grabiner BC, et al. (2007) CARMA3 deficiency abrogates G protein-coupled receptor-induced NF-{kappa}B activation. Genes Dev 21(8):984-96 |
| abstractText | G protein-coupled receptors (GPCRs) play pivotal roles in regulating various cellular functions. Although many GPCRs induce NF-kappaB activation, the molecular mechanism of GPCR-induced NF-kappaB activation remains largely unknown. CARMA3 (CARD and MAGUK domain-containing protein 3) is a scaffold molecule with unknown biological functions. By generating CARMA3 knockout mice using the gene targeting approach, here we show CARMA3 is required for GPCR-induced NF-kappaB activation. Mechanistically, we found that CARMA3 deficiency impairs GPCR-induced IkappaB kinase (IKK) activation, although it does not affect GPCR-induced IKKalpha/beta phosphorylation, indicating that inducible phosphorylation of IKKalpha/beta alone is not sufficient to induce its kinase activity. We also found that CARMA3 is physically associated with NEMO/IKKgamma, and induces polyubiquitination of an unknown protein(s) that associates with NEMO, likely by linking NEMO to TRAF6. Consistently, we found TRAF6 deficiency also abrogates GPCR-induced NF-kappaB activation. Together, our results provide the genetic evidence that CARMA3 is required for GPCR-induced NF-kappaB activation. |
