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Molecules 2018, 23(2), 395; https://doi.org/10.3390/molecules23020395

Proteinaceous Regulators and Inhibitors of Protein Tyrosine Phosphatases

1
Department of Cell Biology, Radboud University Medical Center, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands
2
Department of Biochemistry, Radboud University Medical Center, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands
3
Biomarkers in Cancer Unit, Biocruces Health Research Institute, 48903 Barakaldo, Spain
4
IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
*
Author to whom correspondence should be addressed.
Received: 23 January 2018 / Revised: 9 February 2018 / Accepted: 9 February 2018 / Published: 12 February 2018
(This article belongs to the Special Issue Protein-Tyrosine Phosphatase Inhibitors)
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Abstract

Proper control of the phosphotyrosine content in signal transduction proteins is essential for normal cell behavior and is lost in many pathologies. Attempts to normalize aberrant tyrosine phosphorylation levels in disease states currently involve either the application of small compounds that inhibit tyrosine kinases (TKs) or the addition of growth factors or their mimetics to boost receptor-type TK activity. Therapies that target the TK enzymatic counterparts, the multi-enzyme family of protein tyrosine phosphatases (PTPs), are still lacking despite their undisputed involvement in human diseases. Efforts to pharmacologically modulate PTP activity have been frustrated by the conserved structure of the PTP catalytic core, providing a daunting problem with respect to target specificity. Over the years, however, many different protein interaction-based regulatory mechanisms that control PTP activity have been uncovered, providing alternative possibilities to control PTPs individually. Here, we review these regulatory principles, discuss existing biologics and proteinaceous compounds that affect PTP activity, and mention future opportunities to drug PTPs via these regulatory concepts. View Full-Text
Keywords: biologics; PDZ domain; protein inhibitors; protein tyrosine kinases; protein–protein interaction; regulation of activity; signal transduction biologics; PDZ domain; protein inhibitors; protein tyrosine kinases; protein–protein interaction; regulation of activity; signal transduction
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Hendriks, W.; Bourgonje, A.; Leenders, W.; Pulido, R. Proteinaceous Regulators and Inhibitors of Protein Tyrosine Phosphatases. Molecules 2018, 23, 395.

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