Sonic Hedgehog: Difference between revisions

As with all members of the Hh family, Shh biosynthesis begins with an unusual molecular processing event. Following cleavage of its signal peptide, the Shh precursor prtoein is autocatalytically cleaved into a 19-kDa amino-terminal domain (Shh-N) and a 27-kDa C-terminal domain (Shh-C) <ref> Bumcrot DA, Takada R, McMahon AP. Proteolytic processing yields two secreted forms of sonic hedgehog. 1995 April;15(4);2294-2302</ref>. Spanning residues 24 to 197 in human Shh, Shh-N is responsible for all of the local and long-range signaling activities of Shh. Shh-C possesses an intramolecular transferase activity responsible for covalent attachment of a molecule of cholesterol to the C-terminus of Shh-N. Addition of cholesterol serves to tether Shh-N to the cell membrane, restricting its range of activity to that of local signaling only <ref> Porter JA, Young KE, Beachy PA. Cholesterol modification of hedgehog signalling proteins in animal development. Science. 1996 Oct 11;274:255-259</ref>. Thus, the two domains of Shh are catalytically distinct.