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Ligand-induced formation of p55 and p75 tumor necrosis factor receptor heterocomplexes on intact cells.
J Biol Chem. 1997 Apr 18; 272(16):10784-9.JB

Abstract

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 "ligand passing," 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.

Authors+Show Affiliations

Department of Pathology, Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9099731

Citation

Pinckard, J K., et al. "Ligand-induced Formation of P55 and P75 Tumor Necrosis Factor Receptor Heterocomplexes On Intact Cells." The Journal of Biological Chemistry, vol. 272, no. 16, 1997, pp. 10784-9.
Pinckard JK, Sheehan KC, Schreiber RD. Ligand-induced formation of p55 and p75 tumor necrosis factor receptor heterocomplexes on intact cells. J Biol Chem. 1997;272(16):10784-9.
Pinckard, J. K., Sheehan, K. C., & Schreiber, R. D. (1997). Ligand-induced formation of p55 and p75 tumor necrosis factor receptor heterocomplexes on intact cells. The Journal of Biological Chemistry, 272(16), 10784-9.
Pinckard JK, Sheehan KC, Schreiber RD. Ligand-induced Formation of P55 and P75 Tumor Necrosis Factor Receptor Heterocomplexes On Intact Cells. J Biol Chem. 1997 Apr 18;272(16):10784-9. PubMed PMID: 9099731.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ligand-induced formation of p55 and p75 tumor necrosis factor receptor heterocomplexes on intact cells. AU - Pinckard,J K, AU - Sheehan,K C, AU - Schreiber,R D, PY - 1997/4/18/pubmed PY - 1997/4/18/medline PY - 1997/4/18/entrez SP - 10784 EP - 9 JF - The Journal of biological chemistry JO - J Biol Chem VL - 272 IS - 16 N2 - 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 "ligand passing," 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. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/9099731/Ligand_induced_formation_of_p55_and_p75_tumor_necrosis_factor_receptor_heterocomplexes_on_intact_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(18)40755-7 DB - PRIME DP - Unbound Medicine ER -