Ligand-induced Formation of p55 and p75 Tumor Necrosis Factor Receptor Heterocomplexes on Intact Cells
The p55 and p75 tumor necrosis factor receptors are known to mediate their effects on cells through distinct signaling pathways. Under certain circumstances, the two classes of TNF receptors cooperate with each another to produce enhanced cellular responses. The only molecular mechanism proposed thu...
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Published in | The Journal of biological chemistry Vol. 272; no. 16; pp. 10784 - 10789 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Biochemistry and Molecular Biology
18.04.1997
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Subjects | |
Online Access | Get full text |
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Summary: | The p55 and p75 tumor necrosis factor receptors are known to mediate their effects on cells through distinct signaling pathways.
Under certain circumstances, the two classes of TNF receptors cooperate with each another to produce enhanced cellular responses.
The only molecular mechanism proposed thus far to explain this effect is the process of âligand passing,â whereby TNF is concentrated
at cell surfaces by binding to p75 and then following dissociation from this receptor class binds with high efficiency to
p55. Using the in vivo model of TNF-induced TNF receptor shedding we have uncovered a novel ligand-dependent interaction of the two TNF receptors
that occurs upon exposure of cells to TNF. Using TNF receptor-specific monoclonal antibodies that bind TNF receptors in the
presence or absence of ligand, we report that TNF induces the formation of heterocomplexes consisting of both p55 and p75
TNF receptors. Whereas immunoprecipitates from untreated or human TNF-treated cells formed with either p55 or p75 TNF receptor-specific
monoclonal antibodies contained only the relevant TNF receptor class, anti-p55 or anti-p75 precipitated both receptor types
from murine TNF-treated cells. Ligand-induced complex formation was transient, occurred at physiologically relevant concentrations
of TNF, and occurred with receptors lacking intracellular domains or that contained irrelevant transmembrane domains. Formation
of TNF receptor heterocomplexes may therefore 1) define a novel molecular mechanism of ligand passing and/or 2) contribute
to cooperative TNF receptor signaling via the juxtaposition of the intracellular domains of the two receptor classes and the
signaling proteins that they recruit. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.272.16.10784 |