Reactome | Hh-Np is cleaved by ADAM17 to promote ligand shedding

Hh-Np is cleaved by ADAM17 to promote ligand shedding

Stable Identifier

R-HSA-5362793

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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Hh-Np is cleaved by ADAM17 to promote ligand shedding

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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
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