PAK5-mediated PKM2 phosphorylation is critical for anaerobic glycolysis in endometriosis  

作　　者：Jiayi Lu Xiaoyun Wang Xiaodan Shi Junyi Jiang Lan Liu Lu Liu Chune Ren Chao Lu Zhenhai Yu 

机构地区：[1]Department of Reproductive Medicine,Affiliated Hospital of Shandong Second Medical University,Weifang,261042,China [2]School of Clinical Medicine,Shandong Second Medical University,Weifang,261053,China [3]Center for Reproductive Medicine,Department of Obstetrics and Gynecology,Peking University Third Hospital,Beijing,100191,China

出　　处：《Frontiers of Medicine》2024年第6期1054-1067,F0004,共15页医学前沿(英文版)

基　　金：supported by research grants from the National Natural Science Foundation of China(Nos.81972489 and 82003201);the National Natural Science Foundation of Shandong Province(No.ZR2020YQ58);Shandong Province College Science and Technology Plan Project(No.J17KA254);Projects of medical and health technology development program in Shandong province(No.2018WS057).

摘　　要：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.

关 键 词：PAK5 PKM2 PHOSPHORYLATION ENDOMETRIOSIS GLYCOLYSIS 

分 类 号：R711.71[医药卫生—妇产科学]