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. 2018 Oct 22;19(11):e46589. doi: 10.15252/embr.201846589

Figure 2. Hedgehog signaling in PC .

Figure 2

In the absence of Hh ligands such as Sonic Hh (Shh), the negative regulators Ptch and GPR161 are present on the ciliary membrane. In this state (OFF), suppressor of fused (SuFu) forms a complex with the Gli transcription factors at the tip of the cilium. Upon phosphorylation by the kinases PKA, glycogen synthase kinase 3 (GSK3) and casein kinase 1α (CK1α) 1 at the basal body, Gli is processed in a repressor form (GliR) and migrates into the nucleus, where it represses the transcription of target genes. Ligand binding to Ptch (ON) induces its translocation away from the cilium and promotes the entry of the activating receptor Smo. This process allows the migration of active Gli (GliA) into the nucleus where transcription of Hh target genes is activated. Whether SuFu dissociates from Gli or migrates associated with GliA into the nucleus remains controversial.