Protein tyrosine phosphatases as potential therapeutic targets
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 phos...
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| Published in: | Acta pharmacologica Sinica Vol. 35; no. 10; pp. 1227 - 1246 |
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| Main Authors: | , , , |
| Format: | Journal Article |
| Language: | English |
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London
Nature Publishing Group UK
01-10-2014
Nature Publishing Group |
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| 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, 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. |
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| AbstractList | 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. 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. |
| Author | Rong-jun HE Zhi-hong YU Ruo-yu ZHANG Zhong-yin ZHANG |
| AuthorAffiliation | Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202,USA |
| Author_xml | – sequence: 1 givenname: Rong-jun surname: He fullname: He, Rong-jun organization: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine – sequence: 2 givenname: Zhi-hong surname: Yu fullname: Yu, Zhi-hong organization: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine – sequence: 3 givenname: Ruo-yu surname: Zhang fullname: Zhang, Ruo-yu organization: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine – sequence: 4 givenname: Zhong-yin surname: Zhang fullname: Zhang, Zhong-yin email: zyzhang@iu.edu organization: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25220640$$D View this record in MEDLINE/PubMed |
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| DOI | 10.1038/aps.2014.80 |
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| DocumentTitleAlternate | Protein tyrosine phosphatases as potential therapeutic targets |
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| Keywords | PTP1B Fas associated phosphatase-1 phosphatases of regenerating liver-1 CDC25 mitogen-activated protein kinase phosphatases lymphoid-specific tyrosine phosphatase low molecular weight PTPs striatal enriched tyrosine phosphatases drug target protein tyrosine phosphatases Src homology phosphotyrosyl phosphatase 2 CD45 antigen |
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| Notes | 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. drug target; protein tyrosine phosphatases; PTPIB; Src homology phosphotyrosyl phosphatase 2; lymphoid-specific tyrosinephosphatase; Fas associated phosphatase-1; CD45 antigen; striatal enriched tyrosine phosphatases; mitogen-activated protein kinasephosphatases; phosphatases of regenerating liver-l; low molecular weight PTPs; CDC25 31-1347/R ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 The first two authors contributed equally to this work. |
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| PublicationTitle | Acta pharmacologica Sinica |
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| PublicationYear | 2014 |
| Publisher | Nature Publishing Group UK Nature Publishing Group |
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| Snippet | Protein tyrosine phosphorylation is a key regulatory process in virtually all aspects of cellular functions. Dysregulation of protein tyrosine phosphorylation... |
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| SubjectTerms | 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 |
| Title | Protein tyrosine phosphatases as potential therapeutic targets |
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