Tiganis, Tony, Tonks, Nicholas K (September 2025) Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases. Nature Reviews Molecular Cell Biology. ISSN 1471-0072
Abstract
Aberrations in protein tyrosine phosphorylation-dependent cell signalling contribute to a wide variety of human diseases. Drugs targeting protein tyrosine kinases have had a major impact on human health; by contrast, protein tyrosine phosphatases (PTPs), which serve unique functions and together with protein tyrosine kinases coordinate tyrosine phosphorylation-dependent cell signalling, have been underexploited therapeutically. In this Review, we discuss key breakthroughs in our understanding of how PTPs are regulated, highlight their capacity to coordinate signalling and provide examples of their complex roles in physiology and pathophysiology, including diabetes, obesity and cancer. Also, we discuss the development of PTP-targeted therapeutics that are in clinical trials or poised for clinical translation. We argue that the emergence of this class of enzymes from the shadows lays the foundation for a more complete understanding of the regulation of cell signalling and heralds a new era of drug development opportunities to combat important human diseases.
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