A second tumor necrosis factor receptor gene product can shed a naturally occurring tumor necrosis factor inhibitor

Tadahiko Kohno, Michael T. Brewer, Susan L. Baker, Phillip E. Schwartz, Michael W. King, Karin K. Hale, Charles H. Squires, Robert C. Thompson, James L. Vannice

Research output: Contribution to journalArticle

259 Scopus citations

Abstract

An inhibitor of tumor necrosis factor (TNF) has been isolated from the human histiocytic lymphoma cell line U-937 that is capable of inhibiting both TNF-α and TNF-β. Protein sequencing has verified that it is distinct from a previously described TNF inhibitor that is a soluble fragment of a TNF receptor molecule (TNFrI). The cDNA sequence of this second TNF inhibitor clone suggests that it is also a soluble fragment of a TNF receptor. Expression of this cDNA sequence in COS-7 cells verified that it encodes a receptor for TNF-α (TNFrII) that can give rise to a soluble inhibitor of TNF-α, presumably through proteolytic cleavage. The extracellular domain of TNFrII has significant homology with that of TNFrI and these two receptors share a striking conservation of cysteine residue alignment with the extracellular domain of the nerve growth factor receptor. These three receptor molecules are therefore members of a family of polypeptide hormone receptors.

Original languageEnglish (US)
Pages (from-to)8331-8335
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number21
DOIs
StatePublished - Jan 1 1990
Externally publishedYes

Keywords

  • cDNA cloning
  • Gene expression
  • Lymphotoxin
  • Phorbol 12-myristate 13-acetate
  • Receptor shedding

ASJC Scopus subject areas

  • Genetics
  • General

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