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CD40

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Encyclopedia of Signaling Molecules

Synonyms

Bp50; CDW40; MGC9013; p50; TNFRSF5

Historical Background

CD40, a 50kDa transmembrane member of the tumor-necrosis factor (TNF) receptor (TNFR) superfamily of molecules, plays a key role in adaptive immune responses. This includes contact-mediated signals to B cells from activated T lymphocytes, as well as costimulatory interactions between T cells and other antigen-presenting cells (APC), such as dendritic cells (DC) and macrophages. CD40-mediated interactions between B and T cells make important contributions to the development of an optimal humoral memory response (Bishop 2009).

CD40 lacks intrinsic enzymatic activity and therefore depends on cytoplasmic (CY) adaptor molecules referred to as TNFR-associated factors (TRAFs) for delivery of signals to the cytoplasm. CD40 engagement on B cells stimulates the binding of TRAFs to the CD40 CY domain. This in turn stimulates kinase activity and gene expression pathways that lead to a variety of responses, including B cell survival...

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References

  • Arcipowski KM, Bishop GA. Roles of the kinase TAK1 in TRAF6-dependent signaling by CD40 and its oncogenic viral mimic, LMP1. PLoS One. 2012;7:e42478.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baccam M, Woo S, Vinson C, Bishop GA. CD40-mediated transcriptional regulation of the IL-6 gene in B lymphocytes: Involvement of NF-κB, AP-1, and C/EBP. J Immunol. 2003;170:3099–108.

    Article  CAS  PubMed  Google Scholar 

  • Bishop GA. The many faces of CD40: Multiple roles in normal immunity and disease. Semin Immunol. 2009;21:255–312.

    Article  PubMed  Google Scholar 

  • Bishop GA. The multifaceted roles of TRAFs in the regulation of B cell function. Nat Rev Immunol. 2004;4:775–86.

    Article  CAS  PubMed  Google Scholar 

  • Bishop GA. The power of mAbs as agents of discovery: CD40 revealed as a B lymphocyte costimulator. J Immunol. 2012;188:4127–9. doi:10.4049/jimmunol.1200775.

    Article  CAS  PubMed  Google Scholar 

  • Bishop GA, Hostager BS. The CD40-CD154 interaction in B cell-T cell liaisons. Cytokine Growth Factor Rev. 2003;14:297–309.

    Article  CAS  PubMed  Google Scholar 

  • Bishop GA, Hostager BS. Molecular mechanisms of CD40 signaling. Arch Immun Ther Exper. 2001a;49:129–37.

    CAS  Google Scholar 

  • Bishop GA, Hostager BS. Signaling by CD40 and its mimics in B cell activation. Immunol Res. 2001b;24:97–109.

    Article  CAS  PubMed  Google Scholar 

  • Bishop GA, Hostager BS, Brown KD. Mechanisms of TRAF regulation in B lymphocytes. J Leukoc Biol. 2002;72:19–23.

    CAS  PubMed  Google Scholar 

  • Bishop GA, Moore CR, Xie P, Stunz LL, Kraus ZJ. TRAF proteins in CD40 signaling. Adv Exp Biol Med. 2007;597:131–51.

    Article  Google Scholar 

  • Fang D-F, He K, Wang N, Sang Z, Qiu X, Xu G, et al. NEDD4 ubiquitinates TRAF3 to promote CD40-mediated AKT activation. Nature Comm. 2014;5:1–11. doi:10.1038/ncomms5513.

    CAS  Google Scholar 

  • Graham JP, Arcipowski KM, Bishop GA. Differential B lymphocyte regulation by CD40 and its viral mimic, LMP1. Immunol Rev. 2010;237:226–48.

    Article  CAS  PubMed  Google Scholar 

  • Häcker H, Tseng P-H, Karin M. Expanding TRAF function: TRAF3 as a tri-faced immune regulator. Nat Rev Immunol. 2011;11:457–68.

    Article  PubMed  Google Scholar 

  • Haxhinasto SA, Hostager BS, Bishop GA. Cutting Edge: Molecular mechanisms of synergy between CD40 and the BCR: Role for TRAF2 in receptor interaction. J Immunol. 2002;169:1145–9.

    Article  CAS  PubMed  Google Scholar 

  • Hildebrand JM, Yi Z, Buchta CM, Poovassery JS, Stunz LL, Bishop GA. Roles of TRAF3 and TRAF5 in immune cell function. Immunol Rev. 2011;244:55–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hostager BS. Roles of TRAF6 in CD40 signaling. Immunol Res. 2007;39:105–14.

    Article  CAS  PubMed  Google Scholar 

  • Hostager BS, Bishop GA. CD40-mediated activation of the NF-κB2 pathway. Front Immunol 2013;4:Article 376, 1–4.

    Google Scholar 

  • Hostager BS, Kashiwada M, Colgan J, Rothman PB. HOIP is essential for CD40 signaling. PLoS One. 2011;6:e23061.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hsing Y, Bishop GA. Requirement for NF-κB activation by a distinct subset of CD40-mediated effector functions in B lymphocytes. J Immunol. 1999;162:2804–11.

    CAS  PubMed  Google Scholar 

  • Karin M, Gallagher E. TNFR signaling: ubiquitin-conjugated traffic signals control stop-and-go for MAPK signaling complexes. Immunol Rev. 2009;228:225–40.

    Article  CAS  PubMed  Google Scholar 

  • Lin WW, Hostager BS, Bishop GA. TRAF3, ubiquitination, and B lymphocyte regulation. Immunol Rev. 2015;266:46–55. doi:10.1111/lmr.12299.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miliara S, Gkouskou KK, Sharp TV, Eliopoulos AG. SUMOylation is required for optimal TRAF3 signaling capacity. PLoS One. 2013;8:e80470.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mukundan L, Bishop GA, Head KZ, Zhang L, Wahl LM, Suttles J. TRAF6 is an essential mediator of CD40-activated proinflammatory pathways in monocytes and macrophages. J Immunol. 2005;174:1081–90.

    Article  CAS  PubMed  Google Scholar 

  • Peters AL, Stunz LL, Bishop GA. CD40 and autoimmunity: the dark side of a great activator. Semin Immunol. 2009;21:293–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rowland SR, Tremblay ML, Ellison JM, Stunz LL, Bishop GA, Hostager BS. A novel mechanism for TRAF6-dependent CD40 signaling. J Immunol. 2007;179:4645–53.

    Article  CAS  PubMed  Google Scholar 

  • Sasaki Y, Sano S, Nakahara M, Murata S, Kometani K, Aiba Y, et al. Defective immune responses in mice lacking LUBAC-mediated linear ubiquitination in B cells. EMBO J. 2013;32:2463–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schönbeck U, Libby P. The CD40/CD154 receptor/ligand dyad. Cell Mol Life Sci. 2001;58:4–43.

    Article  PubMed  Google Scholar 

  • Uckun FM, Schieven GL, Dibirdik I, Chandan-Langlie M, Tuel-Ahlgren L, Ledbetter JA. Stimulation of protein tyrosine phosphorylation, phosphoinositide turnover, and multiple previously unidentified ser/thr-specific protein kinases by the pan-BCR CD40/Bp50 at discrete developmental stages of human B-cell ontogeny. J Biol Chem. 1991;266:17478–85.

    CAS  PubMed  Google Scholar 

  • Yi Z, Bishop GA. Regulatory role of CD40 in obesity-induced insulin resistance. Adipocyte. 2014;4. doi:10.4161/adip.32214.

    Google Scholar 

  • Yi Z, Lin WW, Stunz LL, Bishop GA. Roles for TRAF3 in lymphocyte functions. Cytokine Growth Factor Rev. 2014;25:146–56.

    Article  Google Scholar 

  • Zarnegar B, He JQ, Oganesyan G, Hoffmann A, Baltimore D, Cheng G. Unique CD40-mediated biological program in B cell activation requires both type 1 and type 2 NF-κB activation pathways. Proc Natl Acad Sci USA. 2004;101:8108–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Gail A. Bishop .

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Bishop, G.A., Hostager, B.S. (2016). CD40. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_148-1

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  • DOI: https://doi.org/10.1007/978-1-4614-6438-9_148-1

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  • Online ISBN: 978-1-4614-6438-9

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