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PMID: 9435233 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The type 1 receptor (CD120a) is the high-affinity receptor for soluble tumor necrosis factor.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 2 ·1998-01-20 ·Pages 570-5

Grell M, Wajant H, Zimmermann G, Scheurich P

Abstract

Tumor necrosis factor (TNF) can induce a variety of cellular responses at low picomolar concentrations. This is in apparent conflict with the published dissociation constants for TNF binding to TNF receptors in the order of 100-500 pM. To elucidate the mechanisms underlying the outstanding cellular sensitivity to TNF, we determined the binding characteristics of TNF to both human TNF receptors at 37 degrees C. Calculation of the dissociation constant (Kd) from the association and dissociation rate constants determined at 37 degrees C revealed a remarkable high affinity for TNF binding to the 60-kDa TNF type 1 receptor (TNF-R1; Kd = 1.9 x 10(-11) M) and a significantly lower affinity for the 80-kDa TNF type 2 receptor (TNF-R2; Kd = 4.2 x 10(-10) M). The high affinity determined for TNF-R1 is mainly caused by the marked stability of ligand-receptor complexes in contrast to the transient interaction of soluble TNF with TNF-R2. These data can readily explain the predominant role of TNF-R1 in induction of cellular responses by soluble TNF and suggest the stability of the TNF-TNF receptor complexes as a rationale for their differential signaling capability. In accordance with this reasoning, the lower signaling capability of homotrimeric lymphotoxin, compared with TNF, correlates with a lower stability of the lymphotoxin-TNF-R1 complex at 37 degrees C.

MeSH Terms
Antigens, CD/metabolism HeLa Cells Humans Kinetics Receptors, Tumor Necrosis Factor/metabolism Receptors, Tumor Necrosis Factor, Type I Signal Transduction Tumor Necrosis Factor-alpha/metabolism
Chemicals
Antigens, CD Receptors, Tumor Necrosis Factor Receptors, Tumor Necrosis Factor, Type I Tumor Necrosis Factor-alpha
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Grell M
Institute of Cell Biology and Immunology, University of Stuttgart, Germany. Matthias.Grell@po.uni-stuttgart.de
Wajant H
Zimmermann G
Scheurich P
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.2.570
Email
matthias.grell@po.uni-stuttgart.de
Published
1998-01-20
Pages
570-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC18461
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.95.2.570 PMC Full Text View journal details
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