The Structure, Function and Regulation of Protein Tyrosine Phosphatase Receptor Type J and Its Role in Diseases
Protein tyrosine phosphatase receptor type J (PTPRJ), also known as DEP-1, HPTPη, or CD148, belongs to the R3 subfamily of receptor protein tyrosine phosphatases (RPTPs). It was first identified as an antioncogene due to its protein level being significantly downregulated in most epithelial tumors a...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/12/1/8 |
| _version_ | 1797626152810971136 |
|---|---|
| author | Huiting Li Peng Zhang Cencen Liu Yiwei Wang Yan Deng Wei Dong Yang Yu |
| author_facet | Huiting Li Peng Zhang Cencen Liu Yiwei Wang Yan Deng Wei Dong Yang Yu |
| author_sort | Huiting Li |
| collection | DOAJ |
| description | Protein tyrosine phosphatase receptor type J (PTPRJ), also known as DEP-1, HPTPη, or CD148, belongs to the R3 subfamily of receptor protein tyrosine phosphatases (RPTPs). It was first identified as an antioncogene due to its protein level being significantly downregulated in most epithelial tumors and cancer cell lines (e.g., colon, lung, thyroid, breast, and pancreas). PTPRJ regulates mouse optic nerve projection by inhibiting the phosphorylation of the erythropoietin-producing hepatocellular carcinoma (Eph) receptor and abelson murine leukemia viral oncogene homolog 1 (c-Abl). PTPRJ is crucial for metabolism. Recent studies have demonstrated that PTPRJ dephosphorylates JAK2 at positions Y813 and Y868 to inhibit leptin signaling. Akt is more phosphorylated at the Ser473 and Thr308 sites in <i>Ptprj</i><sup>−/−</sup> mice, suggesting that PTPRJ may be a novel negative regulator of insulin signaling. PTPRJ also plays an important role in balancing the pro- and anti-osteoclastogenic activity of the M-CSF receptor (M-CSFR), and in maintaining NFATc1 expression during the late stages of osteoclastogenesis to promote bone-resorbing osteoclast (OCL) maturation. Furthermore, multiple receptor tyrosine kinases (RTKs) as substrates of PTPRJ are probably a potential therapeutic target for many types of diseases, such as cancer, neurodegenerative diseases, and metabolic diseases, by inhibiting their phosphorylation activity. In light of the important roles that PTPRJ plays in many diseases, this review summarizes the structural features of the protein, its expression pattern, and the physiological and pathological functions of PTPRJ, to provide new ideas for treating PTPRJ as a potential therapeutic target for related metabolic diseases and cancer. |
| first_indexed | 2024-03-11T10:06:26Z |
| format | Article |
| id | doaj.art-f5405d524b8c402d8b1f2461821705d5 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T10:06:26Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-f5405d524b8c402d8b1f2461821705d52023-11-16T15:04:49ZengMDPI AGCells2073-44092022-12-01121810.3390/cells12010008The Structure, Function and Regulation of Protein Tyrosine Phosphatase Receptor Type J and Its Role in DiseasesHuiting Li0Peng Zhang1Cencen Liu2Yiwei Wang3Yan Deng4Wei Dong5Yang Yu6Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases), Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, ChinaKey Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases), Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, ChinaPeople’s Hospital of Zhongjiang County, Deyang 618100, ChinaDepartment of Human Anatomy and Histoembryology, School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, ChinaDepartment of Human Anatomy and Histoembryology, School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, ChinaKey Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases), Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, ChinaKey Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases), Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, ChinaProtein tyrosine phosphatase receptor type J (PTPRJ), also known as DEP-1, HPTPη, or CD148, belongs to the R3 subfamily of receptor protein tyrosine phosphatases (RPTPs). It was first identified as an antioncogene due to its protein level being significantly downregulated in most epithelial tumors and cancer cell lines (e.g., colon, lung, thyroid, breast, and pancreas). PTPRJ regulates mouse optic nerve projection by inhibiting the phosphorylation of the erythropoietin-producing hepatocellular carcinoma (Eph) receptor and abelson murine leukemia viral oncogene homolog 1 (c-Abl). PTPRJ is crucial for metabolism. Recent studies have demonstrated that PTPRJ dephosphorylates JAK2 at positions Y813 and Y868 to inhibit leptin signaling. Akt is more phosphorylated at the Ser473 and Thr308 sites in <i>Ptprj</i><sup>−/−</sup> mice, suggesting that PTPRJ may be a novel negative regulator of insulin signaling. PTPRJ also plays an important role in balancing the pro- and anti-osteoclastogenic activity of the M-CSF receptor (M-CSFR), and in maintaining NFATc1 expression during the late stages of osteoclastogenesis to promote bone-resorbing osteoclast (OCL) maturation. Furthermore, multiple receptor tyrosine kinases (RTKs) as substrates of PTPRJ are probably a potential therapeutic target for many types of diseases, such as cancer, neurodegenerative diseases, and metabolic diseases, by inhibiting their phosphorylation activity. In light of the important roles that PTPRJ plays in many diseases, this review summarizes the structural features of the protein, its expression pattern, and the physiological and pathological functions of PTPRJ, to provide new ideas for treating PTPRJ as a potential therapeutic target for related metabolic diseases and cancer.https://www.mdpi.com/2073-4409/12/1/8protein tyrosine phosphatase receptor type J (PTPRJ)antioncogenemetabolic diseasesneurological disorderssignaling pathway |
| spellingShingle | Huiting Li Peng Zhang Cencen Liu Yiwei Wang Yan Deng Wei Dong Yang Yu The Structure, Function and Regulation of Protein Tyrosine Phosphatase Receptor Type J and Its Role in Diseases Cells protein tyrosine phosphatase receptor type J (PTPRJ) antioncogene metabolic diseases neurological disorders signaling pathway |
| title | The Structure, Function and Regulation of Protein Tyrosine Phosphatase Receptor Type J and Its Role in Diseases |
| title_full | The Structure, Function and Regulation of Protein Tyrosine Phosphatase Receptor Type J and Its Role in Diseases |
| title_fullStr | The Structure, Function and Regulation of Protein Tyrosine Phosphatase Receptor Type J and Its Role in Diseases |
| title_full_unstemmed | The Structure, Function and Regulation of Protein Tyrosine Phosphatase Receptor Type J and Its Role in Diseases |
| title_short | The Structure, Function and Regulation of Protein Tyrosine Phosphatase Receptor Type J and Its Role in Diseases |
| title_sort | structure function and regulation of protein tyrosine phosphatase receptor type j and its role in diseases |
| topic | protein tyrosine phosphatase receptor type J (PTPRJ) antioncogene metabolic diseases neurological disorders signaling pathway |
| url | https://www.mdpi.com/2073-4409/12/1/8 |
| work_keys_str_mv | AT huitingli thestructurefunctionandregulationofproteintyrosinephosphatasereceptortypejanditsroleindiseases AT pengzhang thestructurefunctionandregulationofproteintyrosinephosphatasereceptortypejanditsroleindiseases AT cencenliu thestructurefunctionandregulationofproteintyrosinephosphatasereceptortypejanditsroleindiseases AT yiweiwang thestructurefunctionandregulationofproteintyrosinephosphatasereceptortypejanditsroleindiseases AT yandeng thestructurefunctionandregulationofproteintyrosinephosphatasereceptortypejanditsroleindiseases AT weidong thestructurefunctionandregulationofproteintyrosinephosphatasereceptortypejanditsroleindiseases AT yangyu thestructurefunctionandregulationofproteintyrosinephosphatasereceptortypejanditsroleindiseases AT huitingli structurefunctionandregulationofproteintyrosinephosphatasereceptortypejanditsroleindiseases AT pengzhang structurefunctionandregulationofproteintyrosinephosphatasereceptortypejanditsroleindiseases AT cencenliu structurefunctionandregulationofproteintyrosinephosphatasereceptortypejanditsroleindiseases AT yiweiwang structurefunctionandregulationofproteintyrosinephosphatasereceptortypejanditsroleindiseases AT yandeng structurefunctionandregulationofproteintyrosinephosphatasereceptortypejanditsroleindiseases AT weidong structurefunctionandregulationofproteintyrosinephosphatasereceptortypejanditsroleindiseases AT yangyu structurefunctionandregulationofproteintyrosinephosphatasereceptortypejanditsroleindiseases |