Pak5, also known as p21-activated kinase 5, belongs to the PAK-II subfamily. It is a serine/threonine kinase and a downstream effector for Cdc42 and Rac, subfamilies of Rho small GTPases. Pak5 is an important regulator of cell survival, adhesion, and motility, and has been associated with various cellular processes such as anti-apoptosis, proliferation, and cytoskeleton regulation [2].

Knockdown of Pak5 or use of its inhibitor GNE 2861 blocks the development of endometriosis, as also demonstrated in Pak5-knockout mice. This reveals that Pak5 promotes glycolysis by enhancing the protein stability of pyruvate kinase 2 (PKM2) in endometriotic cells, and the phosphorylation of PKM2 at Ser519 by Pak5 mediates endometriosis cell proliferation and metastasis [1]. In breast cancer, Pak5 deficiency represses MMTV-PyVT-driven breast tumorigenesis, indicating its role in breast cancer tumorigenesis [3].

In conclusion, Pak5 plays crucial roles in multiple biological processes and disease conditions. The use of Pak5-knockout mouse models has been instrumental in revealing its functions in endometriosis and breast cancer, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Lu, Jiayi, Wang, Xiaoyun, Shi, Xiaodan, Lu, Chao, Yu, Zhenhai. 2024. PAK5-mediated PKM2 phosphorylation is critical for anaerobic glycolysis in endometriosis. In Frontiers of medicine, 18, 1054-1067. doi:10.1007/s11684-024-1069-3. https://pubmed.ncbi.nlm.nih.gov/39331255/

2. Li, Yu-Kun, Zou, Juan, Ye, Dong-Mei, Luo, Gui-Fang, Zeng, Xi. 2019. Human p21-activated kinase 5 (PAK5) expression and potential mechanisms in relevant cancers: Basic and clinical perspectives for molecular cancer therapeutics. In Life sciences, 241, 117113. doi:10.1016/j.lfs.2019.117113. https://pubmed.ncbi.nlm.nih.gov/31805288/

3. Li, Yang, Xing, Yao, Wang, Xu, Jin, Feng, Li, Feng. . PAK5 promotes RNA helicase DDX5 sumoylation and miRNA-10b processing in a kinase-dependent manner in breast cancer. In Cell reports, 37, 110127. doi:10.1016/j.celrep.2021.110127. https://pubmed.ncbi.nlm.nih.gov/34936874/

4. Wen, Yi-Yang, Zheng, Jun-Nian, Pei, Dong-Sheng. 2014. An oncogenic kinase: putting PAK5 forward. In Expert opinion on therapeutic targets, 18, 807-15. doi:10.1517/14728222.2014.918103. https://pubmed.ncbi.nlm.nih.gov/24869804/