Protein tyrosine phosphatases as potential therapeutic targets

Rong Jun He, Zhi Hong Yu, Ruo Yu Zhang, Zhong-Yin Zhang

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

Protein tyrosine phosphorylation is a key regulatory process in virtually all aspects of cellular functions. Dysregulation of protein tyrosine phosphorylation is a major cause of human diseases, such as cancers, diabetes, autoimmune disorders, and neurological diseases. Indeed, protein tyrosine phosphorylation-mediated signaling events offer ample therapeutic targets, and drug discovery efforts to date have brought over two dozen kinase inhibitors to the clinic. Accordingly, protein tyrosine phosphatases (PTPs) are considered next-generation drug targets. For instance, PTP1B is a well-known targets of type 2 diabetes and obesity, and recent studies indicate that it is also a promising target for breast cancer. SHP2 is a bona-fide oncoprotein, mutations of which cause juvenile myelomonocytic leukemia, acute myeloid leukemia, and solid tumors. In addition, LYP is strongly associated with type 1 diabetes and many other autoimmune diseases. This review summarizes recent findings on several highly recognized PTP family drug targets, including PTP1B, Src homology phosphotyrosyl phosphatase 2(SHP2), lymphoid-specific tyrosine phosphatase (LYP), CD45, Fas associated phosphatase-1 (FAP-1), striatal enriched tyrosine phosphatases (STEP), mitogen-activated protein kinase/dual-specificity phosphatase 1 (MKP-1), phosphatases of regenerating liver-1 (PRL), low molecular weight PTPs (LMWPTP), and CDC25. Given that there are over 100 family members, we hope this review will serve as a road map for innovative drug discovery targeting PTPs.

Original languageEnglish
Pages (from-to)1227-1246
Number of pages20
JournalActa Pharmacologica Sinica
Volume35
Issue number10
DOIs
StatePublished - Oct 1 2014

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Protein Tyrosine Phosphatases
Tyrosine
Phosphoric Monoester Hydrolases
Dual Specificity Phosphatase 1
Phosphorylation
Drug Discovery
Type 1 Diabetes Mellitus
Non-Receptor Type 22 Protein Tyrosine Phosphatase
Therapeutics
Juvenile Myelomonocytic Leukemia
Mitogen-Activated Protein Kinase Phosphatases
Corpus Striatum
Proteins
Oncogene Proteins
Drug Delivery Systems
Nervous System Diseases
Acute Myeloid Leukemia
Pharmaceutical Preparations
Type 2 Diabetes Mellitus
Autoimmune Diseases

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Protein tyrosine phosphatases as potential therapeutic targets. / He, Rong Jun; Yu, Zhi Hong; Zhang, Ruo Yu; Zhang, Zhong-Yin.

In: Acta Pharmacologica Sinica, Vol. 35, No. 10, 01.10.2014, p. 1227-1246.

Research output: Contribution to journalArticle

He, Rong Jun ; Yu, Zhi Hong ; Zhang, Ruo Yu ; Zhang, Zhong-Yin. / Protein tyrosine phosphatases as potential therapeutic targets. In: Acta Pharmacologica Sinica. 2014 ; Vol. 35, No. 10. pp. 1227-1246.
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