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/