PAK5-mediated PKM2 phosphorylation is critical for anaerobic glycolysis in endometriosis.
10.1007/s11684-024-1069-3
- Author:
Jiayi LU
1
;
Xiaoyun WANG
1
;
Xiaodan SHI
2
;
Junyi JIANG
1
;
Lan LIU
1
;
Lu LIU
1
;
Chune REN
3
,
4
;
Chao LU
4
,
5
;
Zhenhai YU
4
,
6
Author Information
1. Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University, Weifang, 261042, China.
2. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.
3. Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University, Weifang, 261042, China. chuneren@
4. com.
5. Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University, Weifang, 261042, China. vincentslu@
6. Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University, Weifang, 261042, China. tomsyu@
- Publication Type:Journal Article
- Keywords:
PAK5;
PKM2;
endometriosis;
glycolysis;
phosphorylation
- MeSH:
Endometriosis/genetics*;
Female;
Animals;
p21-Activated Kinases/genetics*;
Mice;
Phosphorylation;
Glycolysis;
Humans;
Thyroid Hormone-Binding Proteins;
Membrane Proteins/genetics*;
Carrier Proteins/genetics*;
Cell Proliferation;
Mice, Knockout;
Thyroid Hormones/metabolism*;
Pyruvate Kinase/genetics*
- From:
Frontiers of Medicine
2024;18(6):1054-1067
- CountryChina
- Language:English
-
Abstract:
P21-activated kinase 5 (PAK5) belongs to the PAK-II subfamily, which is an important regulator of cell survival, adhesion, and motility. However, the functions of PAK5 in endometriosis remain unclear. Here, PAK5 is strikingly upregulated in endometriosis. Furthermore, the knockdown of PAK5 or its inhibitor GNE 2861 blocks the development of endometriosis, which is equally demonstrated in PAK5-knockout mice. In addition, PAK5 promotes glycolysis by enhancing the protein stability of pyruvate kinase 2 (PKM2) in endometriotic cells, which is a key enzyme for glucose metabolism. Moreover, the phosphorylation of PKM2 at Ser519 by PAK5 mediates endometriosis cell proliferation and metastasis. Collectively, PAK5 plays an indispensable role in endometriosis. Our findings demonstrate that PAK5 is an important target for the treatment of endometriosis.
