Figure 3.

Interplay of the cAMP-PKA axis and Hh signaling in the primary cilium. Shown is a simplified depiction of the Hh on (+Hh) and off (−Hh) states in mammalian cells. Gpr161 and Smoothened (Smo) receptors act as key signal transducer. The involvement of other GPCRs, which impact cAMP and thus Hh signaling, are indicated. In the absence of the Hh ligand, Ptc inhibits Smo signaling. In a PKA dependent-manner, the repressor forms of Gli transcription factors (=Gli-R) are processed. Gli-R prevent the Hh directed gene expression profiles. Upon Hh binding to Ptc, activated Smo is recruited into the cilium, where it counteracts AC activities and Gpr161-PKA signalosomes are exported. The consequence is that the activated transcription factor Gli-A is enriched to promote Hh target gene expression.