Abstract
Lymphoid-tyrosine phosphatase (Lyp), encoded by the PTPN22 gene, is a member of the protein tyrosine phosphatase family enzymes. Human genetics studies have shown that a single-nucleotide polymorphism in PTPN22 is often mutated in patients suffering from autoimmune diseases such as type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosis. Because of its critical role in the regulation of T-cell Receptor (TCR) signaling pathways, Lyp recently emerged as a candidate target for therapy of autoimmune diseases. Herein, we review the structure and splice isoforms of Lyp, the biochemistry of the disease-predisposing allele, discuss the function of the phosphatase in TCR signaling and the association with human autoimmune diseases. Especially, we summarized recent progress in the development of Lyp inhibitors, intending to provide a basis for the Lyp-based treatment of autoimmunity. Moreover, the emphasis and direction for future study of Lyp in autoimmune diseases were prospected.
Keywords: Autoimmune diseases, lymphoid-tyrosine phosphatase, Lyp, PTPs, inhibitor.
Current Drug Targets
Title:Lymphoid-Specific Tyrosine Phosphatase (Lyp): A Potential Drug Target For Treatment of Autoimmune Diseases
Volume: 15 Issue: 3
Author(s): Jintong Du, Yu Qiao, Lele Sun and Xiuwen Wang
Affiliation:
Keywords: Autoimmune diseases, lymphoid-tyrosine phosphatase, Lyp, PTPs, inhibitor.
Abstract: Lymphoid-tyrosine phosphatase (Lyp), encoded by the PTPN22 gene, is a member of the protein tyrosine phosphatase family enzymes. Human genetics studies have shown that a single-nucleotide polymorphism in PTPN22 is often mutated in patients suffering from autoimmune diseases such as type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosis. Because of its critical role in the regulation of T-cell Receptor (TCR) signaling pathways, Lyp recently emerged as a candidate target for therapy of autoimmune diseases. Herein, we review the structure and splice isoforms of Lyp, the biochemistry of the disease-predisposing allele, discuss the function of the phosphatase in TCR signaling and the association with human autoimmune diseases. Especially, we summarized recent progress in the development of Lyp inhibitors, intending to provide a basis for the Lyp-based treatment of autoimmunity. Moreover, the emphasis and direction for future study of Lyp in autoimmune diseases were prospected.
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Cite this article as:
Du Jintong, Qiao Yu, Sun Lele and Wang Xiuwen, Lymphoid-Specific Tyrosine Phosphatase (Lyp): A Potential Drug Target For Treatment of Autoimmune Diseases, Current Drug Targets 2014; 15 (3) . https://dx.doi.org/10.2174/13894501113146660236
DOI https://dx.doi.org/10.2174/13894501113146660236 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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