Bibliographic Details
| Title: |
Multiple allostery in the regulation of PDGFR beta kinase activities |
| Authors: |
Zhang Yanfeng, Wang Meimei, Shao Guangcan, Shang Qingbin, Dong Mengqiu, Qin Xiaohong, Mi Li-Zhi |
| Source: |
Acta Biochimica et Biophysica Sinica, Vol 57, Pp 344-355 (2024) |
| Publisher Information: |
China Science Publishing & Media Ltd., 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Biochemistry
LCC:Genetics |
| Subject Terms: |
allosteric regulation, symmetric dimerization, kinase insert, platelet-derived growth factor receptor beta (PDGFRβ), colony stimulating factor 1 receptor (CSF1R), Biochemistry, QD415-436, Genetics, QH426-470 |
| More Details: |
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). |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1672-9145 |
| Relation: |
https://doaj.org/toc/1672-9145 |
| DOI: |
10.3724/abbs.2024205 |
| Access URL: |
https://doaj.org/article/b311f71e0efd4ebe8bc6b2de6dad34eb |
| Accession Number: |
edsdoj.b311f71e0efd4ebe8bc6b2de6dad34eb |
| Database: |
Directory of Open Access Journals |
