TNF-α is initially synthesized as a 26kDa transmembrane protein (membrane TNF-α), which is processed by proteolytic cleavage known as ectodomain shedding (Tang P et al. 1996). TNF-α-converting enzyme (TACE or ADAM17) mediates the cleavage of TNF-α generating the soluble 17kDa form (Robertshaw HJ & Brennan FM 2005). Inhibition of TACE activity resulted in an accumulation of unprocessed TNF-α on the cell surface of human monocytic cells (THP1) (Tabaka HN et al. 2012). Both membrane-bound and secreted forms of TNF-α are biologically active and may trigger different activities due to their differential capacities to stimulate TNFR1 and TNFR2. TNFR1 is efficiently activated by soluble and membrane TNF-α, TNFR2 signaling, however, is preferentially stimulated by membrane TNF-α while the soluble form has limited activity on this receptor despite efficient binding (Grell M et al. 1995; Grell M et al. 1998).
Kessler, P, Moreira-Tabaka, H, Peluso, J, Dumont, S, Reimund, JM, Hentsch, D, Muller, CD, Vonesch, JL
Robertshaw, HJ, Brennan, FM
metalloendopeptidase activity of ADAM17 [plasma membrane]
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