ArticleProceedings of the National Academy of Sciences of the United States of America1999
Two differently regulated nuclear factor kappaB activation pathways triggered by the cytoplasmic tail of CD40.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 99 citations in OpenAlex.
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- PairK: Pairwise k-mer alignment for quantifying protein motif conservation in disordered regions.Protein science : a publication of the Protein Society · 2025Article
- PairK: Pairwise k-mer alignment for quantifying protein motif conservation in disordered regions.bioRxiv : the preprint server for biology · 2024Article
- NF-kB's contribution to B cell fate decisions.Frontiers in immunology · 2023Review
- Molecular determinants of TRAF6 binding specificity suggest that native interaction partners are not optimized for affinity.Protein science : a publication of the Protein Society · 2022Article
- Molecular basis and therapeutic implications of CD40/CD40L immune checkpoint.Pharmacology & therapeutics · 2021Review
- TNF receptor-associated factor 6 (TRAF6) plays crucial roles in multiple biological systems through polyubiquitination-mediated NF-κB activation.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2021Review
- CD40L membrane retention enhances the immunostimulatory effects of CD40 ligation.Scientific reports · 2020Article
- Integrative Proteomic and Phosphoproteomic Analyses of Granulosa Cells During Follicular Atresia in Porcine.Frontiers in cell and developmental biology · 2020Article
- Efficacy of cytokine-induced killer cells targeting CD40 and GITR.Oncology letters · 2019Article
- Quantification and functional evaluation of CD40L production from the adenovirus vector ONCOS-401.Cancer gene therapy · 2019Article
- Expression of the Phosphatase Ppef2 Controls Survival and Function of CD8Frontiers in immunology · 2019Article
- ZNT7 binds to CD40 and influences CD154-triggered p38 MAPK activity in B lymphocytes-a possible regulatory mechanism for zinc in immune function.FEBS open bio · 2017Article
- Spatiotemporal pattern of TRAF3 expression after rat spinal cord injury.Journal of molecular histology · 2014Article
- Fas-associated factor (Faf1) is a novel CD40 interactor that regulates CD40-induced NF-κB activation via a negative feedback loop.Cell death & disease · 2014Article
- AMPKα1 deficiency amplifies proinflammatory myeloid APC activity and CD40 signaling.Journal of leukocyte biology · 2013Article
- Prohibitins and the cytoplasmic domain of CD86 cooperate to mediate CD86 signaling in B lymphocytes.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Identification and characterization of anti-osteoclastogenic peptides derived from the cytoplasmic tail of receptor activator of nuclear factor kappa B.Journal of bone and mineral metabolism · 2012Article
- TRAF6 activation in multiple myeloma: a potential therapeutic target.Clinical lymphoma, myeloma & leukemia · 2012Review
- Roles of tumor necrosis factor receptor associated factor 3 (TRAF3) and TRAF5 in immune cell functions.Immunological reviews · 2011Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD40 signaling modulates the immune response at least in part by activation of nuclear factor kappaB (NFkappaB). It has been shown that two distinct domains in the CD40 cytoplasmic tail (cyt), namely cyt-N and cyt-C, independently activate NFkappaB. Although four members of the tumor necrosis factor receptor-associated factor (TRAF) family, including TRAF2, TRAF3, TRAF5, and TRAF6, bind to the CD40 cyt, how each TRAF protein contributes to the NFkappaB activation by CD40 is not clear. Here we report that TRAF2, TRAF3, and TRAF5 bind cyt-C, whereas TRAF6 binds cyt-N. cyt-N is conserved poorly between human and mouse CD40, while cyt-C is highly conserved. However, single aa substitution of Glu-235 in cyt-N of human CD40 with Ala abolishes the binding of TRAF6 to cyt-N and NFkappaB activation by cyt-N. Conservation of this Glu between mouse and human CD40 strongly suggests that TRAF6 could link cyt-N to signals essential for CD40-mediated immune response. Furthermore, NFkappaB activation by cyt-C is inhibited by a kinase-negative form of NFkappaB-inducing kinase more efficiently than that by cyt-N, consistent with the result that NFkappaB activation by TRAF2 and TRAF5 is inhibited by a kinase-negative form of NFkappaB-inducing kinase more efficiently than that by TRAF6. These results indicate that NFkappaB activating signals emanating from cyt-N and cyt-C are mediated by the different members of the TRAF family and could be regulated in a distinct manner.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.