Hedgehog and Resident Vascular Stem Cell Fate

Figure 2

Hh signalling in vertebrates. (a) In the absence of Hh, the Hh receptor, Ptch, represses Smo. Sufu binds to the Gli-FL transcription factors, sequestering them in the cytoplasm. Sufu and Kif7 then mediate the phosphorylation of Gli-FL by recruiting PKA, GSK3β, and CK1α. This signals for the proteolytic cleavage of Gli-FL by βTrCP, resulting in the degradation of the C-terminal and formation of Gli-R. Gli-R then localizes to the nucleus and represses the expression of Hh target genes. (b) In the presence of Hh, Hh binds to Ptch, antagonizing its repressor function. Smo becomes phosphorylated by CK1α and GRK2 and promotes β-arrestin and Kif3a-dependent trafficking of Smo to the cilium. With the aid of Kif7, Smo then promotes the disassembly of the Sufu-Gli-FL complex. Gli-FL then localizes to the nucleus to activate target gene expression and is later degraded by Spop.