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Smoothened (Smo), a class Frizzled G protein-coupled receptor (class F GPCR), transduces the Hedgehog (Hh) signal across the cell membrane. The Hh signaling pathway includes both canonical and noncanonical pathways. The canonical Hh pathway functions through major Hh molecules such as Hh ligands, PTCH, Smo, and GLI, whereas the noncanonical Hh pathway involves the activation of Smo or GLI through other pathways. The Hh signaling cascade is initiated by the binding of the Hh protein ligand to its cellular membrane receptor, Patched (PTCH), which relieves PTCH-mediated repression of the seven-transmembrane (7TM) protein Smo. Activated Smo transduces the signal to the GLI family of transcription factors, which translocate to the nucleus to regulate numerous gene products involved in tissue patterning and cell differentiation.
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