Tumor Necrosis Factor (TNF) Receptor Superfamily Member TACI Is a High Affinity Receptor for TNF Family Members APRIL and BLyS

Mast cells are the major effector-cell type for immediate hypersensitivity and other forms of allergic reactions. Expression of 4-1BB, a member of the tumor necrosis factor receptor superfamily, is induced at mRNA and protein levels on stimulation through the high-affinity receptor for immunoglobulin E (IgE; FcϵRI). In this study, we present evidence that agonistic anti-4-1BB antibodies can enhance FcϵRI-induced cytokine production and secretion. Consistent with this, 4-1BB-deficient mast cells exhibit reduced degranulation and cytokine production on FcϵRI stimulation. Analysis of 4-1BB ligand (4-1BBL)-deficient cells supported this notion. As a potential mechanism for these defects, we identified a defect in Ca2+ flux induced by FcϵRI stimulation. The defective Ca2+ flux could be accounted for by the reduced activity of Lyn/Btk/phospholipase C-γ2 pathway and constitutive interactions between 4-1BB and Lyn. Therefore, FcϵRI-inducible 4-1BB plays a costimulatory function together with FcϵRI stimulation.

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Interactions of Tumor Necrosis Factor (TNF) and TNF Receptor Family Members in the Mouse and Human

Journal of Biological Chemistry ◽

10.1074/jbc.m601553200 ◽

2006 ◽

Vol 281 (20) ◽

pp. 13964-13971 ◽

Cited By ~ 280

Author(s):

Claudia Bossen ◽

Karine Ingold ◽

Aubry Tardivel ◽

Jean-Luc Bodmer ◽

Olivier Gaide ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Family Members ◽

Tnf Receptor ◽

Tnf Receptor Family ◽

Necrosis Factor ◽

Receptor Family

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The α and β Subunits of IκB Kinase (IKK) Mediate TRAF2-Dependent IKK Recruitment to Tumor Necrosis Factor (TNF) Receptor 1 in Response to TNF

Molecular and Cellular Biology ◽

10.1128/mcb.21.12.3986-3994.2001 ◽

2001 ◽

Vol 21 (12) ◽

pp. 3986-3994 ◽

Cited By ~ 100

Author(s):

Anne Devin ◽

Yong Lin ◽

Shoji Yamaoka ◽

Zhiwei Li ◽

Michael Karin ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Leucine Zipper ◽

Nuclear Translocation ◽

Ring Finger ◽

Tnf Receptor ◽

Death Domain ◽

Iκb Kinase ◽

Cytokine Tumor Necrosis Factor ◽

Necrosis Factor

ABSTRACT The activation of IκB kinase (IKK) is a key step in the nuclear translocation of the transcription factor NF-κB. IKK is a complex composed of three subunits: IKKα, IKKβ, and IKKγ (also called NEMO). In response to the proinflammatory cytokine tumor necrosis factor (TNF), IKK is activated after being recruited to the TNF receptor 1 (TNF-R1) complex via TNF receptor-associated factor 2 (TRAF2). We found that the IKKα and IKKβ catalytic subunits are required for IKK-TRAF2 interaction. This interaction occurs through the leucine zipper motif common to IKKα, IKKβ, and the RING finger domain of TRAF2, and either IKKα or IKKβ alone is sufficient for the recruitment of IKK to TNF-R1. Importantly, IKKγ is not essential for TNF-induced IKK recruitment to TNF-R1, as this occurs efficiently in IKKγ-deficient cells. Using TRAF2−/− cells, we demonstrated that the TNF-induced interaction between IKKγ and the death domain kinase RIP is TRAF2 dependent and that one possible function of this interaction is to stabilize the IKK complex when it interacts with TRAF2.

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Membrane lymphotoxin-α2β is a novel tumor necrosis factor (TNF) receptor 2 (TNFR2) agonist

Cell Death and Disease ◽

10.1038/s41419-021-03633-8 ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Kirstin Kucka ◽

Isabell Lang ◽

Tengyu Zhang ◽

Daniela Siegmund ◽

Juliane Medler ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Asymmetric Structure ◽

Tnf Receptor ◽

Membrane Bound ◽

Necrosis Factor

AbstractIn the early 1990s, it has been described that LTα and LTβ form LTα2β and LTαβ2 heterotrimers, which bind to TNFR1 and LTβR, respectively. Afterwards, the LTαβ2–LTβR system has been intensively studied while the LTα2β–TNFR1 interaction has been ignored to date, presumably due to the fact that at the time of identification of the LTα2β–TNFR1 interaction one knew already two ligands for TNFR1, namely TNF and LTα. Here, we show that LTα2β interacts not only with TNFR1 but also with TNFR2. We furthermore demonstrate that membrane-bound LTα2β (memLTα2β), despite its asymmetric structure, stimulates TNFR1 and TNFR2 signaling. Not surprising in view of its ability to interact with TNFR2, LTα2β is inhibited by Etanercept, which is approved for the treatment of rheumatoid arthritis and also inhibits TNF and LTα.

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