'Smoothening' the path for hedgehogs

Studies of the HEDGEHOG signalling pathway in Drosophila have revealed a functional link between two genes, cubitus interruptus and patched, whose human homologues are, respectively, a proto-oncogene and a tumour suppressor. While the former has been implicated as a transcription factor, controversy has surrounded the function of the transmembrane protein encoded by the latter. Somewhere in the signal-transduction pathway between these two lies protein kinase A (PKA), and now SMOOTHENED, whose similarity to G-protein-coupled receptors suggests a link with PKA, has also been implicated in the pathway. This article summarizes the current understanding of the pathway and the interactions between these proteins.