The constitutive components and the transduced mechanisms of Hh signaling pathway. A. In the absence of Hh ligand, the latent Gli transcription factors Gli2/3 are bound to a multiprotein complex with the negative regulator Sufu. Phosphorylation of Gli2/3 by PKA, GSK3β and CK1 targets latent Gli proteins to proteasome-dependent repressor formation (Rep-Gli2/Gli3) that cannot activate target gene transcription upon binding to DNA in the nucleus; B. Upon binding of Hh ligand to its receptor Ptch, Ptch translocates out of the primary cilium, losing its ability to inhibit Smo, which moves into the cilium, thus stimulating the pathway and preventing Gli2 and Gli3 cleavage. The activated forms of Gli2 and Gli3 bind to Gli-promoters in the nucleus and stimulate transcription of the ubiquitous mammalian target genes