Fig. 1: Normal activation mechanism of hedgehog signaling pathway.
From: Mechanisms and therapeutic potential of the hedgehog signaling pathway in cancer
A Without HH ligand activation: Ptch1 inhibits Smo, preventing it from translocating to the cilium. SuFu binds with Gli2/3 and moves into the cilium, where Gli2/3 is phosphorylated by CK1, PKA, and GSK3β, causing Gli2/3 to separate from SuFu. Gli2 and Gli3 then cross the nuclear membrane into the nucleus, where they repress the transcription of target genes, with Gli3 being the primary repressor. B With HH ligand activation: The HH secreting cell releases the HH ligand, activating Smo and causing it to translocate to the cilium. SuFu binds with Gli2/3 and moves into the cilium, where Gli2/3 is phosphorylated by EVC and EVC2, causing Gli2/3 to separate from SuFu. Gli3 remains in the cytoplasm, while Gli2 crosses the nuclear membrane into the nucleus, where it initiates the transcription of target genes. Created with BioRender.com.
