Sonic Hedgehog: Difference between revisions

[[Image: SHH SIGNALING PATHWAY.jpg |left| thumb| '''Figure 3.''' The Sonic hedgehog signaling pathway. In the absence of Shh, Patched inhibits Smo. Inhibition of Patched by Shh activates normal developmental processes. [Note: This figure is adapted from references <ref name="Path"/> and <ref name="ShhGli">PMID: 16339192</ref>.]  ]] In the absence of a Shh signal, a 12 transmembrane receptor protein called Patched blocks the function of Smoothened (Smo), a seven-pass transmembrane protein, by keeping it sequestered in an intracellular vesicle (Figure 3)<ref name="ShhGli"/>. When Shh binds to Patched, inhibition of Smo by Patched is relieved. Patched becomes endocytosed, and Smo translocates to the cell surface. In vertebrates, Smo localizes to the surface of the primary cilium, initiating a signaling cascade that leads to the activation of Gli transcription factors <ref name="Path"/>. Present in both the nucleus and cytoplasm, there are three of these regulatory proteins (''Gli1'', ''Gli2'', and ''Gli3''). Following Shh signaling, all three proteins can act as transcriptional activators of Shh target genes. Gli3, however, can act as both an activator and repressor; in the absence of Shh signaling, Gli3 is cleaved by the proteasome, and its truncated form accumulates in the nucleus where it represses transcription of Shh-responsive genes (Figure 3) <ref name="ShhGli"/>.  

    

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