title: A second tumor necrosis factor receptor gene product can shed a naturally occurring tumor necrosis factor inhibitor.
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-alpha and TNF-beta. 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-alpha (TNFrII) that can give rise to a soluble inhibitor of TNF-alpha, 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.
authors.affiliation: Synergen, Inc., Boulder, CO 80301.
authors.forename: T
authors.initials: T
authors.lastname: Kohno
authors.forename: M T
authors.initials: MT
authors.lastname: Brewer
authors.forename: S L
authors.initials: SL
authors.lastname: Baker
authors.forename: P E
authors.initials: PE
authors.lastname: Schwartz
authors.forename: M W
authors.initials: MW
authors.lastname: King
authors.forename: K K
authors.initials: KK
authors.lastname: Hale
authors.forename: C H
authors.initials: CH
authors.lastname: Squires
authors.forename: R C
authors.initials: RC
authors.lastname: Thompson
authors.forename: J L
authors.initials: JL
authors.lastname: Vannice
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D006801:Humans; D008233:Lymphotoxin-alpha / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009363:Neoplasm Proteins; D016133:Polymerase Chain Reaction; D012334:RNA, Neoplasm / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D012689:Sequence Homology, Nucleic Acid; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D008233:Lymphotoxin-alpha; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha