The mechanism dictating which Raf isoform activates the MAPK pathway in melanoma has been unclear. This study now shows cross-talk between the MAPK and cAMP pathways, with B-Raf kinase specifically inhibited through interaction with Ras through a negative feedback loop in melanoma cells. C-Raf is activated through cAMP pathway inhibition by overexpression of PDE4 isoforms. This explains Raf isoform switching and offers a potential new therapeutic approach for melanoma.
- Amélie Marquette
- Jocelyne André
- Nicolas Dumaz
