Cells respond to changes in their environment, to developmental cues and to pathogen aggression through the action of a complex network of proteins. These networks can be split into a multitude of signalling pathways that relay signals from the microenvironment to the cellular components involved in eliciting a specific response. Perturbations in these signalling processes are at the root of multiple pathologies, the most notable of these being cancer. The study of receptor tyrosine kinase (RTK) signalling led to the first description of a mechanism whereby an extracellular signal is transmitted to the nucleus to induce a transcriptional response. Genetic studies conducted in drosophila and nematodes have provided key elements to this puzzle. Here, we briefly discuss the poorly known contribution of these multicellular organisms to our understanding of what has become a prototype in cell signalling as well as to the more recent description of the complex network of regulators that is now known to govern RTK/RAS/ERK signalling.