ROS may modulate receptor tyrosine kinase (RTK) signalling by regulating protein tyrosine phosphatases (PTPs) redox state. When a peptide ligand such as PDGF binds to its receptor RTK on the surface of a non-phagocytic cell (for example HSC/MFs), the signal can involve activation of PI3K and Rac, which in turn will result in activation of membrane NOX and generation of ROS. Within the cell ROS, such as H2O2, may act on a redox-sensitive cysteine residue in the active site of PTPs and transform the -SH group into the oxidized – SOH group (sulphenic acid), thus reversibly inactivating PTPs. Under physiological conditions and with low levels of ROS this change is rapidly reverted by reducing agents, with this transient redox inhibition of PTPs having a relevant role in RTK signalling. However, in conditions in which intracellular ROS are significantly increased, this may lead to more oxidation and then to irreversible changes, with formation at the level of the sensitive cysteine residues of sulphinic and sulphonic acid. These oxidized forms of PTPs are inactive and this will result in long-lasting blocking of PTP-dependent receptor dephosphorylation, allowing a positive reinforcement of RTK downstream signal transduction. The intracellular thiol/disulfide balance potentially plays a relevant role here: cellular levels of GSH or other reducing agents, for example, may operate to revert the sulphenic acid group in the active site of PTP to the thiolate anion, converting PTP back to the active state.