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Cloning and expression of cDNAs for two distinct murine tumor necrosis factor receptors demonstrate one receptor is species specific

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TLDR
MTNF-R2 showed strong specificity for recombinant murine TNF-alpha, suggesting that the various activities of human tumor necrosis factor alpha reported in mice or in murine cell lines are probably mediated by mT NF-R1.
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.

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Citations
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Journal ArticleDOI

Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance

TL;DR: A role for TNF-alpha in obesity and particularly in the insulin resistance and diabetes that often accompany obesity is indicated.
Journal ArticleDOI

An Essential Role for NF-κB in Preventing TNF-α-Induced Cell Death

TL;DR: Reintroduction of RelA into RelA−/− fibroblasts resulted in enhanced survival, demonstrating that the presence ofrelA is required for protection from TNF-α.
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TRADD–TRAF2 and TRADD–FADD Interactions Define Two Distinct TNF Receptor 1 Signal Transduction Pathways

TL;DR: It is shown that TRADD directly interacts with TRAF2 and FADD, signal transducers that activate NF-kappa B and induce apoptosis, respectively, and these two TNFR1-TRADD signaling cascades appear to bifurcate at TRADD.
Journal ArticleDOI

The TNF receptor 1-associated protein TRADD signals cell death and NF-κB activation

Hailing Hsu, +2 more
- 19 May 1995 - 
TL;DR: The discovery of a novel 34 kDa protein, designated TRADD, that specifically interacts with an intracellular domain of TNFR1 known to be essential for mediating programmed cell death shows that the signaling pathways for TNF-induced cell death and NF-κB activation are distinct.
Journal ArticleDOI

Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection.

TL;DR: The TNFRp55 function renders mice resistant to lethal dosages of either lipopolysaccharides or S. aureus enterotoxin B, and the 55 kd TNFR plays a decisive role in the host's defense against microorganisms and their pathogenic factors.
References
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Journal ArticleDOI

DNA sequencing with chain-terminating inhibitors

TL;DR: A new method for determining nucleotide sequences in DNA is described, which makes use of the 2',3'-dideoxy and arabinon nucleoside analogues of the normal deoxynucleoside triphosphates, which act as specific chain-terminating inhibitors of DNA polymerase.
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Journal ArticleDOI

A new method for predicting signal sequence cleavage sites.

TL;DR: A new method for identifying secretory signal sequences and for predicting the site of cleavage between a signal sequence and the mature exported protein is described.
Journal ArticleDOI

An endotoxin-induced serum factor that causes necrosis of tumors

TL;DR: It is proposed that TNF mediates endotoxin-induced tumor necrosis, and that it may be responsible for the suppression of transformed cells by activated macrophages.
Journal ArticleDOI

Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin.

TL;DR: Recombinant tumour necrosis factor can be obtained by expression of its complementary DNA in Escherichia coli and induces the haemorrhagic necrosis of transplanted methylcholanthrene-induced sarcomas in syngeneic mice.
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