Fig. 1. A highly simplified schematic illustrating the central components and the general mechanism of HH signal transduction. In cells not responding to HH (the "OFF" state), PTC — a twelve-transmembrane-domain-containing protein and the receptor for HH ligands — represses the activity of SMO, a G-protein-coupled receptor-like seven-transmembrane-domain-containing protein. The intracellular consequence of this repression is the PKA-mediated inactivation or conversion of the GLI family of transcription factors (CI in Drosophila) into repressors (GLI^Rep) and constitutive repression of HH target genes. On reception of HH through its binding with PTC (the "ON" state), SMO inhibition is somehow relieved and this results in the nuclear accumulation of activated forms of GLIs (GLI^Act) that induce HH target gene transcription. A conserved target is ptc itself, as upregulation of PTC by HH serves to restrict its signalling range. In vertebrates, Gli1, like ptc, also appears to be transcriptionally regulated by HH through the activities of other GLI proteins. For further details and modulations of the pathway see Ingham and McMahon (Ingham and McMahon, 2001).

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