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Protein phosphorylation on tyrosine residues represents an important cell-signaling mechanism, controlled by the combined balanced actions of tyrosine kinases and protein tyrosine phosphatases (PTPs). Regulatory mechanisms of classical PTPs, a cysteine-based subclass of the PTP superfamily that exclusively dephosphorylates phospho-tyrosine in proteins, include changes in expression, phosphorylation, and subcellular localization. Furthermore, a novel negative regulatory mechanism is the reversible oxidation of the conserved catalytic-site cysteine.
Differential regulation of PTPs has recently been demonstrated in vascular tissue remodelling, diabetes, cell differentiation, and cancer development. Thus, targeting PTPs might serve as a novel therapeutic approach altering tyrosine-signaling. Furthermore, accumulating data on the structural basis and protein interaction of PTPs should pave the way for considering PTPs as strategic therapeutic targets in human diseases.
The research focus of our group is the unravelling of the significance of PTPs on distinct regulatory levels, such as post-transcriptional oxidation, expression, and activity in various experimental organ-based and animal models. This includes analyses of transient negative regulation of PTPs by oxidation under conditions of ischemia/reperfusion, and the characterization of PTPs during cerebro-vascular positive outward remodelling. An additional research focus is to investigate the impact of PTPs in models of insulin resistance. Thus, we expect to further identify and establish PTPs as targets for treatment of cerebral occlusive vascular disease and insulin resistance.