Understanding the specificity of receptor tyrosine kinases signaling

Tyrosine kinase receptors (RTKs) represent a large family of transmembrane proteins,1,2 present in all metazoans, whose function is to transduce signals from the extracellular milieu to the inside of the cells. The common features of this protein family are: the extracellular domain, devoted to the binding to the specific receptor ligand, a single transmembrane region, and an intracellular chain featuring the conserved protein tyrosine kinase domain. RTKs control many aspects of cellular physiology both during development and in adult life, such as cell proliferation, migration, survival and differentiation.

Reciprocal control of cell proliferation and migration

In adult tissue the quiescent state of a single cell is maintained by the steady state conditions of its own microenvironment for what concern both cell-cell as well as cell-ECM interaction and soluble factors concentration. Physiological or pathological conditions can alter this quiescent state through an imbalance of both soluble and insoluble factors that can trigger a cellular phenotypic response. The kind of cellular response depends by many factors but one of the most important is the concentration of soluble cytokines sensed by the target cell. In addition, due to the intrinsic plasticity of many cellular types, every single cell is able, in response to the same stimulus, to rapidly switch phenotype supporting minimal changes of microenviromental cytokines concentration. Wound healing is a typical condition in which epithelial, endothelial as well as mesenchymal cells are firstly subjected to activation of their motility in order to repopulate the damaged region and then they show a strong proliferative response in order to successfully complete the wound repair process. This schema constitute the leitmotif of many other physiological or pathological conditions such as development vasculogenesis/angiogenesis as well as cancer outgrowth and metastasis