Meta-Biol

• Pathways

cAMP is generated by the action of adenylate cyclases (reviewed in Sassone-Corsi, 2012). GPR161 is an orphan GPCR that has recently been identified as a negative regulator of Hh signaling that acts by increasing cellular cAMP levels in the absence of ligand. Overexpression of GPR161 increases cellular cAMP levels in a manner that depends on the G alpha s subunit, and depletion of GPR161 results in aberrant Hh signaling and a decrease in the ratio of processed GLI3R (Mukhopadhyay et al, 2013). These data suggest that GPR161 negatively regulates GLI processing in the absence of Hh signal by modulating PKA activity through cAMP levels (Mukhopadhyay et al, 2013; reviewed in Mukhopadhyay and Rohatgi, 2014).