A Lymphotoxin-β-Specific Receptor

Crowe, Paul D.; VanArsdale, Todd; Walter, Barbara; Ware, Carl F.; Hession, Catherine; Ehrenfels, Barbara; Browning, Jeffrey L.; Din, Wenie S.; Goodwin, Raymond G.; Smith, Craig A.

doi:10.1126/science.8171323

Cited by 369 publications

(222 citation statements)

References 38 publications

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“…In this study we showed that TAPI also blocks the release of Steel factor, type IIIL-1R and IL-2Rcx from transfected COS-7 cells. The finding that the release of the soluble forms of all these molecules can be strongly accelerated by PMA ( [5,13]; this study) and can be blocked by TAPI suggests that a common mechanism is involved, possibly one (or a few) metalloprotease(s) with a broad substrate specificity. This view is also supported by results obtained with CHO cells and a mutant cell line deficient in shedding of TGFa and ß-amyloid precursor protein [30].…”

Section: Resultsmentioning

confidence: 96%

“…No consensus amino acid sequence has been found at the proteolytic cleavage sites of cytokine receptor and growth factor precursors identified so far [1,2]. It was demonstrated that the presence or absence of the cytoplasmic domains of the IL-6R [3] and the p60 TNFR [4] had no effect on shedding of these two proteins, whereas in the case of the p80 TNFR [5] the intracellular part of the molecule influenced the generation of the soluble receptor. Furthermore it has been found that the Cterminal valine residue of the cytoplasmic tail of TGFcc is critical for the release of this growth factor [6].…”

Section: Introductionmentioning

confidence: 94%

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Further evidence for a common mechanism for shedding of cell surface proteins

et al. 1997

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Pro-TNFa, Steel factor, type IIIL-1R and IL-2Ra were expressed in COS-7 cells and the generation of their soluble forms was examined. The release of all four proteins was strongly stimulated by the phorbol ester PMA and completely blocked by a hydroxamate-based inhibitor of metalloproteases. COS-7 cell membranes were found to cleave various synthetic pro-TNFa peptides with the same specificity as a partially purified TNFot converting enzyme purified from human monocytic cells, suggesting that the same enzyme may be responsible for at least some of the COS-7 cell shedding activity.

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Section: Resultsmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 94%

Further evidence for a common mechanism for shedding of cell surface proteins

et al. 1997

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“…Soluble TNFP binds to the same receptors and thus is likely to have similar biologic effects as TNFa (10). However, it has recently been shown that TNFP (or lymphotoxin-a) can exist in a membrane-associated form (23). When complexed with lymphotoxin-P, it binds to a distinct receptor.…”

Section: Discussionmentioning

confidence: 99%

Patterns of expression of tumor necrosis factor α, tumor necrosis factor β, and their receptors in synovia of patients with juvenile rheumatoid arthritis and juvenile spondylarthropathy

Grom

Murray

Luyrink

et al. 1996

Arthritis & Rheumatism

160

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Objective. To assess the expression of tumor necrosis factor α (TNF α), TNF β, and their receptors in synovia of patients with juvenile rheumatoid arthritis (JRA) and juvenile spondylarthropathy (JSpA), and to determine similarities with and differences from adult RA.Methods. Twenty‐eight synovial tissue samples from patients with JRA, 6 from patients with JSpA, and 6 from patients with RA, selected for the presence of inflammatory infiltrates, were analyzed for the expression of TNF α, TNF β, and their receptors (p55 and p75 TNFR), utilizing the dual approach of reverse transcriptase—polymerase chain reaction and immunohistochemistry analysis.Results. The presence of both TNF α and TNF β expression was demonstrated in most JRA and JSpA tissues, although samples from patients with pauci‐articular JRA had somewhat lesser amounts of these cytokines. TNF β expression correlated significantly with the occurrence of lymphocytic aggregates in tissues. Staining with monoclonal antibodies specific for the p55 and p75 receptors revealed that a diverse range of cell types expressed the receptors, with the most intense p55 staining on vascular endothelial cells. In the vast majority of synovial tissues, far greater numbers of cells expressed the p55 form of the receptor than the p75 form.Conclusion. JRA and JSpA synovia are characterized by the presence of TNF α, TNF β, and cells expressing TNFR. These findings provide further evidence that TNF, through autocrine/paracrine mechanisms, may amplify local inflammation, leading to joint destruction. The prominence of TNF β in the synovium in particular subgroups of JRA patients and in JSpA patients may be a distinguishing feature of these diseases.

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“…In the case of LT␣, this occurs through association with another TNF family member, membrane-bound LT␤, to form the LT␣1␤2 heterotrimer (36). By contrast with LT␣, the LT␣1␤2 heterotrimer signals exclusively via a specific receptor (37), the LT␤ receptor (LT␤R), which is present on nonlymphoid cells (38). Although TNF is expressed by many cell types, LT expression is restricted to activated T and B lymphocytes and NK cells; within the CD4 ϩ population LT is expressed by Th1 effector cells (39,40).…”

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confidence: 99%

Membrane Lymphotoxin Is Required for the Development of Different Subpopulations of NK T Cells

Elewaut¹,

Brossay²,

Santee

et al. 2000

The Journal of Immunology

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The development of lymphoid organs requires membrane-bound lymphotoxin (LT), a heterotrimer containing LTα and LTβ, but the effects of LT on T cell function have not been characterized extensively. Upon TCR cross-linking in vitro, splenocytes from both LTα−/− and LTβ−/− mice failed to produce IL-4 and IL-10 due to a reduction in NK T cells. Concordantly, LTα−/− and LTβ−/− mice did not respond to the lipoglycan α-galactosylceramide, which is presented by mouse CD1 to Vα14+ NK T cells. Interestingly, both populations of NK T cells, including those that are mouse CD1 dependent and α-galactosylceramide reactive and those that are not, were affected by disruption of the LTα and LTβ genes. NK T cells were not affected, however, in transgenic mice in which LT signaling is blocked, beginning on day 3 after birth, by expression of a soluble decoy LTβ receptor. This suggests that membrane-bound LT is critical for NK T cells early in ontogeny, but not for the homeostasis of mature cells.

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A Lymphotoxin-β-Specific Receptor

Cited by 369 publications

References 38 publications

Further evidence for a common mechanism for shedding of cell surface proteins

Further evidence for a common mechanism for shedding of cell surface proteins

Patterns of expression of tumor necrosis factor α, tumor necrosis factor β, and their receptors in synovia of patients with juvenile rheumatoid arthritis and juvenile spondylarthropathy

Membrane Lymphotoxin Is Required for the Development of Different Subpopulations of NK T Cells

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