Protein tyrosine phosphatases as potential therapeutic targets

• Published in: Acta pharmacologica Sinica 2014-10, Vol.35 (10), p.1227-1246
• Main Authors: He, Rong-jun, Yu, Zhi-hong, Zhang, Ruo-yu, Zhang, Zhong-yin
• Format: Article
• Language: English
• Subjects: 2型糖尿病; Animals; Biomedical and Life Sciences; Biomedicine; Drug Discovery - methods; Humans; Immunology; Internal Medicine; Medical Microbiology; Pharmacology/Toxicology; Phosphorylation - drug effects; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Protein Tyrosine Phosphatases - antagonists & inhibitors; Protein Tyrosine Phosphatases - metabolism; Review; Vaccine; 促分裂原活化蛋白激酶; 治疗; 自身免疫性疾病; 药物发现; 蛋白酪氨酸磷酸化; 蛋白酪氨酸磷酸酶; 骨髓性白血病
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2014.80

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, PTPIB 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 I diabetes and many other autoimmune diseases. This review summarizes recent findings on several highly recognized PTP family drug targets, including PTPIB, 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.