A second tumor necrosis factor receptor gene product can shed a naturally occurring tumor necrosis factor inhibitor.
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.
Kohno
T
T
Synergen, Inc., Boulder, CO 80301.
Brewer
M T
MT
Baker
S L
SL
Schwartz
P E
PE
King
M W
MW
Hale
K K
KK
Squires
C H
CH
Thompson
R C
RC
Vannice
J L
JL
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*
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