Stk24-KO Mouse

Stk24, also known as MST3, belongs to the germinal center kinase III subfamily. It is involved in multiple biological functions, including the regulation of various signaling pathways like MEKK3, AKT-PD-L1, and STAT3/VEGFA, and plays a role in maintaining vessel stability, cell proliferation, migration, and immune modulation [1,2,4,5]. Genetic models such as knockout (KO) and conditional knockout (CKO) mouse models are valuable for studying Stk24.

In KO/CKO mouse models, deletion of Stk24/25 in endothelial cells led to defects in vascular patterning, CCM lesion formation, and impaired angiogenesis [1]. Stk24-deficient mice developed severe high-fat diet-induced metabolic disorders and insulin insensitivity due to NLRP3 inflammasome activation in adipose tissue macrophages [3]. In addition, in tumor models, deficiency of Stk24 in tumor cells attenuated tumor growth, relying on cytotoxic CD8+ T and NK cells [4].

In conclusion, Stk24 is crucial for maintaining normal physiological functions. Its dysregulation is associated with diseases such as cerebral cavernous malformation, obesity-associated metabolic disorders, and cancer. The study of Stk24 using KO/CKO mouse models has provided insights into its role in these disease conditions, facilitating a better understanding of the underlying mechanisms and potentially leading to new therapeutic strategies.

References:

1. Yang, Xi, Wu, Shi-Ting, Gao, Rui, Wang, Lu, Zheng, Xiangjian. 2023. Release of STK24/25 suppression on MEKK3 signaling in endothelial cells confers cerebral cavernous malformation. In JCI insight, 8, . doi:10.1172/jci.insight.160372. https://pubmed.ncbi.nlm.nih.gov/36692953/

2. Li, Yadong, Liu, Yanhu, Wang, Kun, Tan, Zhenguo, Chen, Yijiang. 2023. STK24 Promotes Progression of LUAD and Modulates the Immune Microenvironment. In Mediators of inflammation, 2023, 8646088. doi:10.1155/2023/8646088. https://pubmed.ncbi.nlm.nih.gov/37181807/

3. Qin, Qiang, Shou, Jia'nan, Li, Mengjie, Meng, Hua, Wang, Xiaojian. . Stk24 protects against obesity-associated metabolic disorders by disrupting the NLRP3 inflammasome. In Cell reports, 35, 109161. doi:10.1016/j.celrep.2021.109161. https://pubmed.ncbi.nlm.nih.gov/34038725/

4. Wang, Ning, Jiang, Yu, Li, Mengjie, Lin, Wenlong, Wang, Xiaojian. 2024. Protein Kinase STK24 Promotes Tumor Immune Evasion via the AKT-PD-L1 Axis. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2304342. doi:10.1002/advs.202304342. https://pubmed.ncbi.nlm.nih.gov/38229183/

5. Lai, Senyan, Wang, Dao, Sun, Wei, Cao, Xiaonian. 2023. Serine/threonine-protein kinase STK24 induces tumorigenesis by regulating the STAT3/VEGFA signaling pathway. In The Journal of biological chemistry, 299, 102961. doi:10.1016/j.jbc.2023.102961. https://pubmed.ncbi.nlm.nih.gov/36720310/