Reactome | alpha-secretase cleaves the p75NTR extracellular domain

alpha-secretase cleaves the p75NTR extracellular domain

Stable Identifier

R-HSA-193679

Type

Reaction [transition]

Species

Homo sapiens

Compartment

extracellular region, plasma membrane

ReviewStatus

5/5

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alpha-secretase cleaves the p75NTR extracellular domain

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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
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
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
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