Model of the endosomal KRas traffic and signaling. EGF binding triggers endocytosis of the EGFR and downstream signaling molecules to the early endosomal compartment. There, Ras signaling modules settle to elicit signal outputs. HRas is ubiquitinated and is recycled back to the PM, whereas KRas is sorted en route to LEs/MVBs. Once there, KRas can be GTP loaded, thus being able to recruit effectors such as Raf1, which initiates the MAPK signaling cascade on this compartment. Finally, KRas down-regulation/degradation may occur in the late endosomal/lysosomal compartment. CCV, clathrin-coated vesicle.