FIGURE 1.

A simplified display of the Hedgehog signaling pathway. (A) In the absence of Hedgehog ligand, full-length Gli is phosphorylated by protein kinase A, glycogen synthase kinase-3, and casein kinase 1. This leads to proteolytic cleavage of the full-length Gli into Gli repressor. Gli repressor represses the expression of target genes, (B) after binding of Hedgehog ligand, Smoothened protein is phosphorylated by protein kinase A and casein kinase 1. The inhibitory effect of Sufu is removed and Gli activator is formed. Gli activator induces the transcription of target genes. Red symbols represent the inhibitory effect, and green arrows show the activating effect. Hh - Hedgehog; Ptch - Patched; Smo - Smoothened; Gli - glioma-associated oncogene; GliFL - full-length Gli; GliA - Gli activator; GliR - Gli repressor; CK1 - casein kinase 1; PKA - protein kinase A; GSK3 - glycogen synthase kinase-3.