ReviewCell Biology

The Hedgehog Signal Transduction Network

Science Signaling  16 Oct 2012:
Vol. 5, Issue 246, pp. re6
DOI: 10.1126/scisignal.2002906

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Gloss

Members of the conserved Hedgehog (Hh) family of secreted proteins play fundamental roles during embryonic development and homeostasis of adult tissues. Hh signal transduction uses an unusual derepression mechanism, in which Hh binding to its receptor component Patched (Ptc) inhibits the capacity of Ptc to repress the heterotrimeric guanine nucleotide–binding protein–coupled receptor Smoothened (Smo). Activation of Smo is accomplished through phosphorylation and subcellular translocation from intracellular vesicles to the plasma membrane and, in vertebrates, also to the primary cilium. This Review focuses primarily on the signaling modules that are set in motion by binding of Hh to Ptc: the “canonical” pathway through which Smo promotes activation of the Gli family of transcription factors, the noncanonical type I pathway in which Ptc modulates cell proliferation and survival independently of Smo, and the noncanonical type II pathway by which Smo regulates the actin cytoskeleton through G inhibitory proteins and small guanosine triphosphatases.