= Tumor necrosis factor receptor 2
= TNFR2
{c}
{synonym}
Tumor necrosis factor receptor 2, abbreviated TNFR2, is a cell-surface <receptor (biochemistry)> for <tumor necrosis factor>. In humans the encoding <gene> is TNFRSF1B; the protein is also known as the p75 receptor or CD120b. It is distinct from the p55 receptor, TNFR1. A <cytokine> and its <receptor (biochemistry)> are different molecules: one supplies a signal and the other provides a binding and response apparatus.<TNFRSF1B in NCBI Gene>[Human gene 7133, official nomenclature, aliases and Summary]{ref}
The <transmembrane protein> has an extracellular ligand-binding portion, a membrane-spanning segment and an intracellular portion involved in <signal transduction>. Binding at the outside and a downstream cellular response are separate experimental observations. A receptor-binding measurement alone does not establish whether a particular cell proliferates, survives or dies.
A motivating molecular experiment used direct expression screening: a human lung-fibroblast <cDNA> library was screened with radiolabeled <tumor necrosis factor> alpha. <C. A. Smith> and colleagues isolated a clone encoding an integral membrane protein of 461 <amino acids>; the expressed receptor also bound TNF-beta. Its predicted cysteine-rich external region connected it to a broader receptor family.<A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins by C. A. Smith and others>[Abstract, expression library, radiolabeled ligand and predicted extracellular region]{ref} This combines a functional binding screen with sequence evidence, rather than identifying a receptor from a name alone.
<Etanercept> provides a useful engineered comparison. It joins the extracellular ligand-binding portion of the human p75 receptor to an <Fc region> of <immunoglobulin G> subclass 1, making a soluble dimeric <fusion protein>.<Enbrel prescribing information in DailyMed>[Sections 11 and 12.1, p75 extracellular region/Fc composition and ligand interception]{ref} This retains a ligand-catching surface while omitting the native membrane attachment and intracellular signaling machinery. Its ligand capture therefore does not mean that it reproduces a membrane TNFR2 signal.
An experimental comparison can measure binding and cellular response separately, using otherwise matched cells with and without the receptor and controlling for other TNF-binding receptors. A change in labeled-ligand binding tests one part of the mechanism; a change in a specified downstream readout tests another. The receptor's presence alone cannot substitute for either measurement.
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