Protein tyrosine phosphatases as potential therapeutic targets

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

Research output: Contribution to journalReview article

146 Scopus citations

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 (US)
Pages (from-to)1227-1246
Number of pages20
JournalDevelopment (Basingstoke)
Volume57
Issue number1
DOIs
StatePublished - Sep 25 2014

Keywords

  • CD45 antigen
  • CDC25
  • Fas associated phosphatase-1
  • PTP1B
  • Src homology phosphotyrosyl phosphatase 2
  • drug target
  • low molecular weight PTPs
  • lymphoid-specific tyrosine phosphatase
  • mitogen-activated protein kinase phosphatases
  • phosphatases of regenerating liver-1
  • protein tyrosine phosphatases
  • striatal enriched tyrosine phosphatases

ASJC Scopus subject areas

  • Geography, Planning and Development
  • Development

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