Internalization of receptor tyrosine kinases (RTKs) is crucial for RTK signaling and cellular responses such as cell migration. This work shows that CD44v6 mediates the internalization of the RTK Met and traffics together with Met through endosomal compartments suggesting that CD44v6 is required for Met-signaling from endosomes. The RTK VEGFR-2 also interacts with CD44v6. However Met and VEGFR-2 are activated with strikingly different kinetics suggesting a different mechanism of internalization