Tfg (Trk fused gene) is a Carma-1/IKKgamma interacting protein involved in CD40-induced canonical NF-KB signaling

  • Carma-1 is required for B cell receptor-/CD40- and T cell receptor-/CD28-induced B- and T-cell activation via JNK and NF-betaB. In B cells, Carma-1 becomes phosphorylated by PKCbeta, leading to its oligomerization. Subsequent Bcl10 binding induces IKKbeta-activation and, thereby, canonical NF-KB signalling. Despite these findings it is still unknown how exactly Carma-1 is connected to the plasma membrane and to the IKK-complex. Therefore, we purified Carma-1 complexes from mouse CH12 B cells using anti-Carma-1 affinity columns. Mass spectrometric analyses of the column eluates demonstrated the presence of Carma-1 as well as three previously uncharacterized adaptor proteins in B cells, one of which was the Trk-fused gene (Tfg), an adaptor protein containing PB1 and coiledcoil domains. Whereas Tfg was originally identified as fusion partner of oncogenic Trk tyrosine kinase mutants, the normal cellular homologue of Tfg has so far not been described in B cells. However, Tfg has been shown in other systems to interact with IKKgamma and to enhance TNFinduced NF-KB activation. Tfg and Carma-1 co-localized at the plasma membrane and perinuclear structures in B cells. We further corroborated the interactions of Tfg, IKKgamma and Carma-1 by Blue Native gel electrophoresis, where Carma-1 and Tfg formed a 0.7–1 MDa complex. Ectopic expression of Tfg increased the molecular mass of IKKgamma complexes, fused IKKgamma, Bcl10 and Carma-1 complexes to a ~2 MDa complex, and increased basal and CD40-induced canonical activity of NF-KB and IKKbeta. In contrast, shRNA-mediated silencing of Tfg decreased CD40-induced IKKbeta activity. Very interestingly, in primary B cells, highest expression of Tfg was detected in marginal zone and B1 B cells, and Carma-1 and Tfg formed complexes in these B cells. Since Carma-1 is required for marginal zone B cell and B1 B cell development, we suggest that a functional interaction between Carma-1 and Tfg contributes to development and maintenance of these cells by means of canonical NF-KB signals.

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Metadaten
Author:Marcus Grohmann, Ingo Hermann, Martin Hampel, Michael Karas, Hubert Kalbacher, Hans-Martin Jäck, Dirk Mielenz
URN:urn:nbn:de:hebis:30-64164
DOI:https://doi.org/10.1186/1478-811X-7-S1-A4
ISSN:1478-811X
Parent Title (English):Cell communication and signaling
Publisher:Biomed Central
Place of publication:London
Document Type:Article
Language:English
Date of Publication (online):2009/04/24
Date of first Publication:2009/02/26
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Contributing Corporation:12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes, Weimar, Germany. 29–31 October 2008
Release Date:2009/04/24
Volume:7
Issue:(Suppl 1):A4
Page Number:1
First Page:1
Last Page:1
Note:
© 2009 Grohmann et al; licensee BioMed Central Ltd.
Source:From 12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes Weimar, Germany. 29–31 October 2008 ; Cell Communication and Signaling 2009, 7(Suppl 1):A4 ; doi:10.1186/1478-811X-7-S1-A4 ; http://www.b
HeBIS-PPN:212160133
Institutes:Biochemie, Chemie und Pharmazie / Pharmazie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Sammlung Biologie / Sondersammelgebiets-Volltexte
Licence (German):License LogoDeutsches Urheberrecht