The Regulation of Lipid Binding and Kinase Activities of EphA2 Kinase Domain by Its Adjacent SAM Domain
10.13865/j.cnki.cjbmb.2022.05.1060
- Author:
Xia WU
1
;
Qian-Gou CHEN
1
;
Yue WANG
1
;
Wei LIU
1
Author Information
1. Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University, The Hong Kong University of Science and Technology Medical Center
- Publication Type:Journal Article
- Keywords:
erythropoietin-producing hepatocellular (Eph receptor);
kinase activity;
liposome;
SAM domain;
tyrosine kinase domain
- From:
Chinese Journal of Biochemistry and Molecular Biology
2022;38(7):892-898
- CountryChina
- Language:Chinese
-
Abstract:
The erythropoietin-producing hepatocellular receptor (Eph receptor) family is the largest subfamily in the receptor tyrosine kinase (RTK) families which mediates cell morphology, adhesion, movement, proliferation, survival, and differentiation by its bidirectional signals coupled with Ephrin ligands. EphA2 receptor is an important isoform which is involved in the pathological changes in cataract, breast cancer, etc. Previous studies found that the kinase domain of the EphA2 receptor binds to the plasma membrane, and its kinase activity is regulated by the plasma membrane. However, it is still unclear that the impact of the adjacent SAM domain on the membrane binding and kinase activities of kinase domain. In this study we purified the cytoplasmic kinase-SAM tandem of the EphA2 receptor by co-expression with the phosphatase PTP1B 1-301 fragment. Our results showed that the SAM domain of EphA2 receptor can further enhance the interaction between the kinase domain and liposomes (4 mg/mL) by 6 folds (P<0. 001). And the phosphorylation of kinase-SAM tandem can enhance its lipid (4 mg/mL) binding ability by 2. 5 folds (P < 0. 05). In addition, the lipid binding ability and tyrosine phosphorylation activities of kinase domain are mutual promoted, which creating a positive feedback loop in the two biological processes. In conclusion, our studies indicate that the kinase domain and the adjacent SAM domain can function as an intact unit, whose lipid binding ability and kinase activity are quite different from the individual kinase domain. Therefore, our results provide a biochemical basis for better understanding of the regulation mechanism of other Eph receptors in its kinase domain.
