Multiple allostery in the regulation of PDGFR beta kinase activities
Platelet-derived growth factor receptor beta (PDGFRβ), a type III receptor tyrosine kinase (RTK) with a featured kinase insert, regulates important cellular functions. Dysregulation of PDGFRβ is associated with cardiovascular and fibrosis diseases. Thus, its kinase activity needs to be precisely reg...
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2024-11-01
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| Series: | Acta Biochimica et Biophysica Sinica |
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| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2024205 |
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| author | Zhang Yanfeng Wang Meimei Shao Guangcan Shang Qingbin Dong Mengqiu Qin Xiaohong Mi Li-Zhi |
| author_facet | Zhang Yanfeng Wang Meimei Shao Guangcan Shang Qingbin Dong Mengqiu Qin Xiaohong Mi Li-Zhi |
| author_sort | Zhang Yanfeng |
| collection | DOAJ |
| description | Platelet-derived growth factor receptor beta (PDGFRβ), a type III receptor tyrosine kinase (RTK) with a featured kinase insert, regulates important cellular functions. Dysregulation of PDGFRβ is associated with cardiovascular and fibrosis diseases. Thus, its kinase activity needs to be precisely regulated under physiological conditions. Early studies demonstrated that its kinase is autoinhibited by its juxtamembrane segment and activated by transphosphorylation. However, additional mechanisms are required for the comprehensive regulation of the receptor kinase. Herein, we provide evidence that dimerization of activated kinases, autoinhibition by the kinase insert, and dimerization of inactive kinase, all contribute to the regulation of the receptor kinase. Moreover, we find such multiple allosteric regulation is also conserved in other type III RTKs, including colony stimulating factor 1 receptor (CSF1R). Impaired allosteric regulation of CSF1R is associated with malfunctions of microglia and demyelination of neurons in hereditary diffuse leukoencephalopathy with spheroids (HDLS). |
| format | Article |
| id | doaj-art-b311f71e0efd4ebe8bc6b2de6dad34eb |
| institution | DOAJ |
| issn | 1672-9145 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj-art-b311f71e0efd4ebe8bc6b2de6dad34eb2025-08-20T03:06:44ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452024-11-015734435510.3724/abbs.202420520d259ccMultiple allostery in the regulation of PDGFR beta kinase activitiesZhang Yanfeng0Wang Meimei1Shao Guangcan2Shang Qingbin3Dong Mengqiu4Qin Xiaohong5Mi Li-Zhi6["School of Life Sciences, Tianjin University, Tianjin 300072, China"]["School of Life Sciences, Tianjin University, Tianjin 300072, China"]["National Institute of Biological Sciences, Beijing 102206, China"]["School of Life Sciences, Tianjin University, Tianjin 300072, China"]["National Institute of Biological Sciences, Beijing 102206, China"]["School of Life Sciences, Tianjin University, Tianjin 300072, China"]["School of Life Sciences, Tianjin University, Tianjin 300072, China"]Platelet-derived growth factor receptor beta (PDGFRβ), a type III receptor tyrosine kinase (RTK) with a featured kinase insert, regulates important cellular functions. Dysregulation of PDGFRβ is associated with cardiovascular and fibrosis diseases. Thus, its kinase activity needs to be precisely regulated under physiological conditions. Early studies demonstrated that its kinase is autoinhibited by its juxtamembrane segment and activated by transphosphorylation. However, additional mechanisms are required for the comprehensive regulation of the receptor kinase. Herein, we provide evidence that dimerization of activated kinases, autoinhibition by the kinase insert, and dimerization of inactive kinase, all contribute to the regulation of the receptor kinase. Moreover, we find such multiple allosteric regulation is also conserved in other type III RTKs, including colony stimulating factor 1 receptor (CSF1R). Impaired allosteric regulation of CSF1R is associated with malfunctions of microglia and demyelination of neurons in hereditary diffuse leukoencephalopathy with spheroids (HDLS).https://www.sciengine.com/doi/10.3724/abbs.2024205allosteric regulationsymmetric dimerizationkinase insertplatelet-derived growth factor receptor beta (PDGFRβ)colony stimulating factor 1 receptor (CSF1R) |
| spellingShingle | Zhang Yanfeng Wang Meimei Shao Guangcan Shang Qingbin Dong Mengqiu Qin Xiaohong Mi Li-Zhi Multiple allostery in the regulation of PDGFR beta kinase activities Acta Biochimica et Biophysica Sinica allosteric regulation symmetric dimerization kinase insert platelet-derived growth factor receptor beta (PDGFRβ) colony stimulating factor 1 receptor (CSF1R) |
| title | Multiple allostery in the regulation of PDGFR beta kinase activities |
| title_full | Multiple allostery in the regulation of PDGFR beta kinase activities |
| title_fullStr | Multiple allostery in the regulation of PDGFR beta kinase activities |
| title_full_unstemmed | Multiple allostery in the regulation of PDGFR beta kinase activities |
| title_short | Multiple allostery in the regulation of PDGFR beta kinase activities |
| title_sort | multiple allostery in the regulation of pdgfr beta kinase activities |
| topic | allosteric regulation symmetric dimerization kinase insert platelet-derived growth factor receptor beta (PDGFRβ) colony stimulating factor 1 receptor (CSF1R) |
| url | https://www.sciengine.com/doi/10.3724/abbs.2024205 |
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