Figure 1.

Background color represents the extracellular ligand gradient. A) Cell far away from the gradient source senses a relatively low ligand concentration. The limited and localized RTK activation induce in turn a primitive formation of submembrane signaling complex that starts organizing focal adhesion structure and induce cellular cytoskeleton remodeling, leading to progressive cellular polarization along the gradient. Local RTK chlatrin-mediated endocytosis of active receptors is the event that promotes and maintains the cyclic process of directional cell migration. B) When migrating cell arrives in a area in which cytokine concentration reaches the "mitotic" threshold the number of activated RTKs increases. Hence, the environmental relative loss of asymmetry is reflected by a not localized RTKs activation that, in turn, induce the loss of cellular asymmetry that stops the migrating process. In addition, the massive RTKs activation leads to triggering of an additional endocytotic route (RME) that relocates RTKs prevalently to the endosomal compartment changing radically the active intracellular signaling modules. The RTKs endosomal signaling is responsible for the activation of the vast transcriptional programme that ultimately leads to mitosis.