Hh-Np is cleaved by ADAM17 to promote ligand shedding

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
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

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
21664575 Sonic hedgehog shedding results in functional activation of the solubilized protein

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

Dev. Cell 2011
19176481 Heparan sulfate-modulated, metalloprotease-mediated sonic hedgehog release from producing cells

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

J. Biol. Chem. 2009
23118222 An emerging role of Sonic hedgehog shedding as a modulator of heparan sulfate interactions

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

J. Biol. Chem. 2012
Catalyst Activity

metalloendopeptidase activity of ADAM17 [plasma membrane]

Inferred From
Cite Us!