Research ArticleDevelopmental Biology

Hedgehog induces formation of PKA-Smoothened complexes to promote Smoothened phosphorylation and pathway activation

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Science Signaling  01 Jul 2014:
Vol. 7, Issue 332, pp. ra62
DOI: 10.1126/scisignal.2005414

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PKA Switches Partners to Promote Hedgehog Signaling

Hedgehog is a secreted protein that controls developmental patterning and cell fate specification. Hedgehog binds to the transmembrane receptor Patched to relieve inhibition of the seven-transmembrane protein Smoothened (Smo), which in turn activates the transcription factor Ci by inhibiting its phosphorylation by the kinase PKA. Li et al. found that, in fruit flies, activated Smo directly bound to and was phosphorylated by the catalytic subunit of PKA. Phosphorylated Smo recruited more of the catalytic subunit of PKA, which prevented the interaction between PKA and Ci, enabling Ci to activate Hedgehog-regulated genes. Thus, this switching of PKA-substrate interactions controls activation of Hedgehog signaling.