Tumor necrosis factor receptor 2

Tumor necrosis factor receptor 2, abbreviated TNFR2, is a cell-surface receptor 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 are different molecules: one supplies a signal and the other provides a binding and response apparatus.^[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.^[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.^[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.