alpha-secretase cleaves the p75NTR extracellular domain

Stable Identifier
R-HSA-193679
Type
Reaction [transition]
Species
Homo sapiens
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alpha-secretase (ADAM17) is a metalloprotese that has the ability to cleave the p75NTR extracellular domain, in proximity of the transmembrane region. The cleaved extracellular domain is shed from the cell membrane, whereas the rest of the protein, the C-terminal fragment, stays anchored to the membrane. The released extracellular domain represents a binding protein for many potential ligands, including neurotrophins, pro-neurotrophin precursors, beta-amyloid. Shedding of the p75NTR extracellular region can be both constituve and stimulated. The constitutive shedding is dependent on signalling via the p38 MAP kinase. Shedding can be stimulated by the phorbol ester PMA, acting through protein kinase C and ERK activation, and by a tyrosine phosphatase inhibitor. Activation of TRKA by NGF (or TRKB by BDNF) also induces release of the p75NTR extracellular domain. The alpha-secretase cleavage is required for the subsequent cleavage by gamma-secretase.

Literature References
PubMed ID Title Journal Year
12913006 Regulated intramembrane proteolysis of the p75 neurotrophin receptor modulates its association with the TrkA receptor

Jung, KM, Tan, S, Landman, N, Petrova, K, Murray, S, Lewis, R, Kim, PK, Kim, DS, Ryu, SH, Chao, MV, Kim, TW

J Biol Chem 2003
15701642 Cleavage of p75 neurotrophin receptor by alpha-secretase and gamma-secretase requires specific receptor domains

Zampieri, N, Xu, CF, Neubert, TA, Chao, MV

J Biol Chem 2005
12843241 Proteolytic processing of the p75 neurotrophin receptor and two homologs generates C-terminal fragments with signaling capability

Kanning, KC, Hudson, M, Amieux, PS, Wiley, JC, Bothwell, M, Schecterson, LC

J Neurosci 2003
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Catalyst Activity
Title
metallopeptidase activity of ADAM 17 metalloprotease (Zn cofactor) [plasma membrane]
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Activity
Orthologous Events
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