TNF-alpha is cleaved by ADAM17 (TACE)

Stable Identifier
R-HSA-3371385
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

TNF-alpha is initially synthesized as a 26kDa transmembrane protein (membrane TNF-alpha), which is processed by proteolytic cleavage known as ectodomain shedding (Tang P et al. 1996). TNF-alpha-converting enzyme (TACE or ADAM17) mediates the cleavage of TNF-alpha generating the soluble 17kDa form (Robertshaw HJ & Brennan FM 2005). Inhibition of TACE activity resulted in an accumulation of unprocessed TNF-alpha on the cell surface of human monocytic cells (THP1) (Tabaka HN et al. 2012). Both membrane-bound and secreted forms of TNF-alpha 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-alpha, TNFR2 signaling, however, is preferentially stimulated by membrane TNF-alpha while the soluble form has limited activity on this receptor despite efficient binding (Grell M et al. 1995; Grell M et al. 1998).

Literature References
PubMed ID Title Journal Year
15556967 Release of tumour necrosis factor alpha (TNFalpha) by TNFalpha cleaving enzyme (TACE) in response to septic stimuli in vitro

Robertshaw, HJ, Brennan, FM

Br J Anaesth 2005
22479555 Unlike for human monocytes after LPS activation, release of TNF-? by THP-1 cells is produced by a TACE catalytically different from constitutive TACE

Moreira-Tabaka, H, Peluso, J, Vonesch, JL, Hentsch, D, Kessler, P, Reimund, JM, Dumont, S, Muller, CD

PLoS ONE 2012
Participants
Participant Of
hasEvent
Catalyst Activity
Catalyst Activity
Title
metalloendopeptidase activity of ADAM17 [plasma membrane]
Physical Entity
Activity
Orthologous Events
Authored
Reviewed
Created