| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
,
,¶
* Interdisciplinary Graduate Program in Immunology,
Department of Microbiology,
Department of Internal Medicine,
Holden Comprehensive Cancer Center, and
¶ Veterans Affairs Medical Center, Iowa City, IA 52242
Engagement of CD40 on murine B cells by its ligand CD154 induces the binding of TNFR-associated factors (TRAFs) 1, 2, 3, and 6, followed by the rapid degradation of TRAFs 2 and 3. TRAF degradation occurs in response to signaling by other TNFR superfamily members, and is likely to be a normal regulatory component of signaling by this receptor family. In this study, we found that receptor-induced TRAF degradation limits TRAF2-dependent CD40 signals to murine B cells. However, TRAFs 1 and 6 are not degraded in response to CD40 engagement, despite their association with CD40. To better understand the mechanisms underlying differential TRAF degradation, mixed protein domain TRAF chimeras were analyzed in murine B cells. Chimeras containing the TRAF2 zinc (Zn) domains induced effective degradation, if attached to a TRAF domain that binds to the PXQXT motif of CD40. However, the Zn domains of TRAF3 and TRAF6 could not induce degradation in response to CD40, regardless of the TRAF domains to which they were attached. Our data indicate that TRAF2 serves as the master regulator of TRAF degradation in response to CD40 signaling, and this function is dependent upon both the TRAF Zn domains and receptor binding position.
This article has been cited by other articles:
|
|
 |
|
  A. Dupoux, J. Cartier, S. Cathelin, R. Filomenko, E. Solary, and L. Dubrez-Daloz cIAP1-dependent TRAF2 degradation regulates the differentiation of monocytes into macrophages and their response to CD40 ligand Blood, January 1, 2009; 113(1): 175 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Qiao, M. Lei, Z. Li, Y. Sun, A. Minto, Y.-X. Fu, H. Ying, R. J. Quigg, and J. Zhang Negative Regulation of CD40-Mediated B Cell Responses by E3 Ubiquitin Ligase Casitas-B-Lineage Lymphoma Protein-B J. Immunol., October 1, 2007; 179(7): 4473 - 4479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Rowland, M. M. Tremblay, J. M. Ellison, L. L. Stunz, G. A. Bishop, and B. S. Hostager A Novel Mechanism for TNFR-Associated Factor 6-Dependent CD40 Signaling J. Immunol., October 1, 2007; 179(7): 4645 - 4653. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. T. Thieu, E. T. Nguyen, B. P. McCarthy, H. A. Bruns, R. Kapur, C.-H. Chang, and M. H. Kaplan IL-4-stimulated NF-{kappa}B activity is required for Stat6 DNA binding J. Leukoc. Biol., August 1, 2007; 82(2): 370 - 379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-F. Lu, C. L. Ahonen, E. F. Lind, V. S. Raman, W. J. Cook, L.-L. Lin, and R. J. Noelle The in vivo function of a noncanonical TRAF2-binding domain in the C-terminus of CD40 in driving B-cell growth and differentiation Blood, July 1, 2007; 110(1): 193 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Munroe and G. A. Bishop A Costimulatory Function for T Cell CD40 J. Immunol., January 15, 2007; 178(2): 671 - 682. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Xie, B. S. Hostager, M. E. Munroe, C. R. Moore, and G. A. Bishop Cooperation between TNF Receptor-Associated Factors 1 and 2 in CD40 Signaling J. Immunol., May 1, 2006; 176(9): 5388 - 5400. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
