title: Cloning and expression of cDNAs for two distinct murine tumor necrosis factor receptors demonstrate one receptor is species specific.
abstract: Complementary DNA clones encoding two distinct tumor necrosis factor receptors were isolated from a mouse macrophage cDNA library. The cDNA for murine tumor necrosis factor receptor type 1 (mTNF-R1) predicts a mature polypeptide of 425 amino acids that is 64% identical to its human counterpart, whereas the cDNA of murine tumor necrosis factor receptor type 2 (mTNF-R2) predicts a mature protein of 452 amino acids that is 62% identical to human tumor necrosis factor receptor type 2. The two murine tumor necrosis factor receptors have limited sequence homology (approximately 20% identity) in their extracellular regions but no apparent similarity in their cytoplasmic portions. Northern (RNA) analysis indicates a single 2.6-kilobase (kb) transcript for mTNF-R1; a 3.6-kb and a more predominant 4.5-kb transcript are observed for mTNF-R2. A human cell line transfected with either mTNF-R1 or mTNF-R2 expression vectors specifically bound 125I-labeled recombinant murine tumor necrosis factor alpha (TNF-alpha). Although mTNF-R1 had a similar affinity for both recombinant murine TNF-alpha and human TNF-alpha, mTNF-R2 showed strong specificity for recombinant murine TNF-alpha. This result suggests that the various activities of human tumor necrosis factor alpha reported in mice or in murine cell lines are probably mediated by mTNF-R1.
authors.affiliation: Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080.
authors.forename: M
authors.initials: M
authors.lastname: Lewis
authors.forename: L A
authors.initials: LA
authors.lastname: Tartaglia
authors.forename: A
authors.initials: A
authors.lastname: Lee
authors.forename: G L
authors.initials: GL
authors.lastname: Bennett
authors.forename: G C
authors.initials: GC
authors.lastname: Rice
authors.forename: G H
authors.initials: GH
authors.lastname: Wong
authors.forename: E Y
authors.initials: EY
authors.lastname: Chen
authors.forename: D V
authors.initials: DV
authors.lastname: Goeddel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D004273:DNA, Neoplasm / Q000235:genetics* / Q000302:isolation & purification; D005354:Fibrosarcoma; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins / Q000378:metabolism; D012513:Sarcoma, Experimental; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D004273:DNA, Neoplasm; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha