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Review
. 2024 Jul 1;16(7):888.
doi: 10.3390/pharmaceutics16070888.

From Tyrosine Kinases to Tyrosine Phosphatases: New Therapeutic Targets in Cancers and Beyond

Yu Zhou  1 , Zhimeng Yao  1   2 , Yusheng Lin  1   3 , Hao Zhang  1   4   5
Affiliations
Review

From Tyrosine Kinases to Tyrosine Phosphatases: New Therapeutic Targets in Cancers and Beyond

Yu Zhou et al. Pharmaceutics. .

Abstract

Protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) regulate the level of tyrosine phosphorylation in proteins. PTKs are key enzymes that catalyze the transfer of an ATP phosphoric acid to a tyrosine residue on target protein substrates. Protein tyrosine phosphatases (PTPs) are responsible for the dephosphorylation of tyrosine residues and play a role in countering PTK overactivity. As widespread oncogenes, PTKs were once considered to be promising targets for therapy. However, tyrosine kinase inhibitors (TKIs) now face a number of challenges, including drug resistance and toxic side effects. Treatment strategies now need to be developed from a new perspective. In this review, we assess the current state of TKIs and highlight the role of PTPs in cancer and other diseases. With the advances of allosteric inhibition and the development of multiple alternative proprietary drug strategies, the reputation of PTPs as "undruggable" targets has been overturned, and they are now considered viable therapeutic targets. We also discuss the strategies and prospects of PTP-targeted therapy, as well as its future development.

Keywords: drug resistance; immune responses; nervous system; protein tyrosine kinases; protein tyrosine phosphatases; tumor suppressor.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Balance of tyrosine residue phosphorylation status in target proteins and their regulation by protein tyroTsine phosphatases (PTPs) and protein tyrosine kinases (PTKs).
Figure 2
Figure 2
PTPs either directly target PTKs or affect multiple downstream pathways. PTPs can directly dephosphorylate PTKs, such as epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and platelet-derived growth factor receptor (PDGFR). Additionally, PTPs can regulate pathways affected by PTKs by dephosphorylating components in the Janus kinase/signal transducer and activator of transcription (JAK/STAT), phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT), mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), Jun N-terminal kinase (JNK), and nuclear factor-kappa B (NF-κB) pathways. Furthermore, PTPs can regulate programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling.
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