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Fig. 1. The Hedgehog pathway in Drosophila and vertebrates. The
Hedgehog (Hh) pathway in Drosophila (A,B) and in vertebrates (C,D) in
the absence (A,C) or presence (B,D) of the Hh ligand. (A) In the
absence of Hh, Ptc prevents the cell-surface localization of Smo, and Ci forms
a complex with Cos2, Fu and Sufu, which targets Ci for proteolytic processing
into the repressor form (CiR). (B) In the presence of high
levels of Hh ligand, Ptc inhibition is relieved; Smo accumulates at the plasma
membrane and forms a complex with Cos2 and Fu through its C-terminal tail; Ci
is activated. (C) In the absence of Hh, Ptch1 prevents the accumulation
of Smo in cilia, possibly through the action of a small molecule. Gli3 is
processed into a repressor form (Gli3R) in a cilia-dependent
manner. The activation of all Gli proteins is inhibited by Sufu, Iguana (for
zebrafish) and probably Cos2. (D) In the presence of high levels of Hh
ligand, Ptch1 inhibition is relieved; Smo is targeted to cilia and activates
Gli proteins in a cilia-dependent manner. Gli3 processing is also inhibited.
p, phosphorylation; PKA, protein kinase A.