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. 2017 Apr 5;8:14805. doi: 10.1038/ncomms14805

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Copyright © 2017, The Author(s)

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(a) In the control setting, tethering between mTNF and TNF receptors (TNFR) provides the structural basis for strain to elicit a reverse signal through mTNF that links to ERK1/2. (b) Etanercept (ETN) which lacks intrinsic activity, interferes with mTNF/TNFR tethering and hence, reverse signalling. (c) Soluble TNF (sTNF) competes with mTNF for TNFR binding, which also interferes with mTNF/TNFR tethering and hence, reverse signalling. (d) The soluble TNFR1 fragment (sTNFR1-Fc) interferes with mTNF/TNFR tethering, but stimulates a reverse signal through its intrinsic activity.