Fig. 1

In the absence of Hh ligands, the PTCH receptor sequesters SMO in a cytoplasmic vesicle. GLI proteins are bound in a complex in the cytoplasm with negative regulators SUFU and KIF7, which target the GLI proteins for phosphorylation by PKA, CK1, and GSK3β inducing the repressive form of GLI proteins. Upon DHH, IHH, or SHH binding to PTCH, PTCH relieves its inhibition on SMO, which then translocates to the primary cilium of the cell and mediates the dissociation of GLI proteins from SUFU and KIF7, allowing localization of GLI proteins to the nucleus where they bind DNA and regulate the transcription of their target genes