Srpk2-KO Mouse

Srpk2, short for serine-arginine protein kinase 2, is a key kinase involved in multiple biological processes. It phosphorylates serine-arginine rich proteins, playing a role in pre-mRNA splicing, which is crucial for gene expression regulation. It is associated with pathways related to lipid metabolism, inflammation, and viral replication, and is of great biological importance as it impacts cell fate, proliferation, and differentiation [3,4,5]. Genetic models such as gene knockout can be valuable for studying its functions.

In HepG2 cells, SRPK2-knockout suppressed the phosphorylation of hepatitis B core protein (Cp), indicating its importance in the HBV life cycle as it mediates Cp phosphorylation and capsid assembly [1]. In BV2 microglia, enhancing SRPK2 expression led to pro-inflammatory activation, while SRPK2 deficiency alleviated the cytotoxic effects of stimuli on HT22 cells, suggesting its role in the inflammatory response in Alzheimer's disease [2]. In FGF21 knockout mice, silencing SRPK2 rescued alcohol-induced splicing dysregulation and liver injury, highlighting its role in alcohol-associated liver disease [4].

In conclusion, Srpk2 is essential for processes like pre-mRNA splicing, viral capsid assembly, microglia activation, and lipogenesis in alcohol-associated liver disease. Gene knockout models have been instrumental in revealing its roles in HBV-related liver diseases, Alzheimer's disease, and alcohol-associated liver disease, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Yip, Ryan Pak Hong, Kwok, Doris Ching Ying, Lai, Louis Tung Faat, Lau, Wilson Chun Yu, Ngo, Jacky Chi Ki. 2024. SRPK2 Mediates HBV Core Protein Phosphorylation and Capsid Assembly via Docking Interaction. In PLoS pathogens, 20, e1011978. doi:10.1371/journal.ppat.1011978. https://pubmed.ncbi.nlm.nih.gov/38324561/

2. Tian, Ziqi, Zeng, Wenfang, Yan, Cuihuan, Yao, Xiaoguang, Li, Si. 2022. SRPK2 Expression and Beta-Amyloid Accumulation Are Associated With BV2 Microglia Activation. In Frontiers in integrative neuroscience, 15, 742377. doi:10.3389/fnint.2021.742377. https://pubmed.ncbi.nlm.nih.gov/35153686/

3. Tan, Wei, Jiang, Pei, Zhang, Wanjun, Qin, Weijie, Pei, Huadong. 2021. Posttranscriptional regulation of de novo lipogenesis by glucose-induced O-GlcNAcylation. In Molecular cell, 81, 1890-1904.e7. doi:10.1016/j.molcel.2021.02.009. https://pubmed.ncbi.nlm.nih.gov/33657401/

4. Li, Guannan, Chen, Hanqing, Shen, Feng, Musi, Nicolas, Zang, Mengwei. 2023. Targeting hepatic serine-arginine protein kinase 2 ameliorates alcohol-associated liver disease by alternative splicing control of lipogenesis. In Hepatology (Baltimore, Md.), 78, 1506-1524. doi:10.1097/HEP.0000000000000433. https://pubmed.ncbi.nlm.nih.gov/37129868/

5. McClellan, Bryan, Gries, Paul, Harlow, Brittany, Jolly, Christopher, deGraffenried, Linda. 2022. An IGF-1R-mTORC1-SRPK2 signaling Axis contributes to FASN regulation in breast cancer. In BMC cancer, 22, 976. doi:10.1186/s12885-022-10062-z. https://pubmed.ncbi.nlm.nih.gov/36096767/