Hh-Np is cleaved by ADAM17 to promote ligand shedding

Stable Identifier
R-HSA-5362793
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Hh-Np can be untethered from the plasma membrane of the secreting cell by ADAM17-mediated cleavage of the lipidated N- and C-termini (Dierker et al, 2009; Ohlig et al, 2011; Ohlig et al, 2012). Shedding of SHH Np from the plasma membrane is abrogated by siRNA depletion of ADAM17, as well as in the presence of metalloprotease inhibitors or mutation of the ADAM17 catalytic E406 residue (Dierker et al, 2009). ADAM17-mediated cleavage is stimulated by heparin sulphate and likely occurs in the context of a HSPG-SHH complex although specific HSPGs have not been identified (Dierker et al, 2009). Cleavage of the cholesterol- and palmitoyl-modified termini is suggested to promote a SHH conformation that is competent to bind to the Patched receptor (Ohlig et al, 2011).

Literature References
PubMed ID Title Journal Year
19176481 Heparan sulfate-modulated, metalloprotease-mediated sonic hedgehog release from producing cells

Dierker, T, Dreier, R, Petersen, A, Bordych, C, Grobe, K

J. Biol. Chem. 2009
21664575 Sonic hedgehog shedding results in functional activation of the solubilized protein

Ohlig, S, Farshi, P, Pickhinke, U, van den Boom, J, Höing, S, Jakuschev, S, Hoffmann, D, Dreier, R, Schöler, HR, Dierker, T, Bordych, C, Grobe, K

Dev. Cell 2011
23118222 An emerging role of Sonic hedgehog shedding as a modulator of heparan sulfate interactions

Ohlig, S, Pickhinke, U, Sirko, S, Bandari, S, Hoffmann, D, Dreier, R, Farshi, P, Götz, M, Grobe, K

J. Biol. Chem. 2012
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
metalloendopeptidase activity of ADAM17 [plasma membrane]
Physical Entity
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Created