Prkca-KO Mouse

Prkca, encoding protein kinase C alpha, is a Th17-cell-selective kinase. Protein kinase C alpha is involved in multiple cellular signaling pathways, which are crucial for various biological processes such as cell growth, differentiation, and apoptosis [3].

In rheumatic heart disease (RHD), there is hypomethylation at the promoter and 5' terminal of Prkca, accompanied by high Prkca expression and down-regulated lncRNA Prkca-AS1. Prkca-AS1 binds to the Prkca promoter via its 5' terminal and interacts with DNMT1 via its 3' terminal, suggesting a novel DNA methylation-mediated regulatory mechanism of Prkca transcription [1]. In papillary glioneuronal tumors (PGNT), the SLC44A1-Prkca fusion is a characteristic alteration and a potential biomarker [2,8]. In chordoid gliomas, a recurrent Prkca D463H mutation is a hallmark, strongly associated with the activation of the protein translation initiation (EIF2) pathway, and the mutant enhances the proliferation of relevant cells of origin [4,6]. In multiple sclerosis, variations in Prkca expression and alternative splicing are associated with disease susceptibility [3,5]. Also, SNPs in Prkca-HIF1A-GLUT1 are potentially associated with diabetic kidney disease in the Chinese Han population [7].

In conclusion, Prkca is essential in multiple signaling pathways. Studies on Prkca-related mutations, fusions, and epigenetic regulations in various diseases like RHD, PGNT, chordoid gliomas, multiple sclerosis, and diabetic kidney disease, contribute to understanding the molecular pathogenesis of these diseases. These insights may potentially lead to the development of novel diagnostic and therapeutic strategies.

References:

1. Xie, Zan, Wang, Qianli, Hu, Shaojuan. . Coordination of PRKCA/PRKCA-AS1 interplay facilitates DNA methyltransferase 1 recruitment on DNA methylation to affect protein kinase C alpha transcription in mitral valve of rheumatic heart disease. In Bioengineered, 12, 5904-5915. doi:10.1080/21655979.2021.1971482. https://pubmed.ncbi.nlm.nih.gov/34482802/

2. Nagaishi, Masaya, Nobusawa, Sumihito, Matsumura, Nozomi, Yokoo, Hideaki, Nakazato, Yoichi. 2015. SLC44A1-PRKCA fusion in papillary and rosette-forming glioneuronal tumors. In Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 23, 73-75. doi:10.1016/j.jocn.2015.04.021. https://pubmed.ncbi.nlm.nih.gov/26260115/

3. Paraboschi, Elvezia M, Rimoldi, Valeria, Soldà, Giulia, Duga, Stefano, Asselta, Rosanna. 2014. Functional variations modulating PRKCA expression and alternative splicing predispose to multiple sclerosis. In Human molecular genetics, 23, 6746-61. doi:10.1093/hmg/ddu392. https://pubmed.ncbi.nlm.nih.gov/25080502/

4. Yao, Kun, Duan, Zejun, Du, Zunguo, Sun, Lingyan, Qi, Xueling. . PRKCA D463H Mutation in Chordoid Glioma of the Third Ventricle: A Cohort of 16 Cases, Including Two Cases Harboring BRAFV600E Mutation. In Journal of neuropathology and experimental neurology, 79, 1183-1192. doi:10.1093/jnen/nlaa107. https://pubmed.ncbi.nlm.nih.gov/33085976/

5. Saarela, Janna, Kallio, Suvi P, Chen, Daniel, Hudson, Thomas J, Peltonen, Leena. 2006. PRKCA and multiple sclerosis: association in two independent populations. In PLoS genetics, 2, e42. doi:. https://pubmed.ncbi.nlm.nih.gov/16596167/

6. Rosenberg, Shai, Simeonova, Iva, Bielle, Franck, Huillard, Emmanuelle, Sanson, Marc. 2018. A recurrent point mutation in PRKCA is a hallmark of chordoid gliomas. In Nature communications, 9, 2371. doi:10.1038/s41467-018-04622-w. https://pubmed.ncbi.nlm.nih.gov/29915258/

7. Huang, Yan, Jin, Li, Yu, Hairong, Hu, Cheng, Liu, Zhihong. 2020. SNPs in PRKCA-HIF1A-GLUT1 are associated with diabetic kidney disease in a Chinese Han population with type 2 diabetes. In European journal of clinical investigation, 50, e13264. doi:10.1111/eci.13264. https://pubmed.ncbi.nlm.nih.gov/32394523/

8. Hou, Yanghao, Pinheiro, Jorge, Sahm, Felix, von Deimling, Andreas, Bertero, Luca. 2019. Papillary glioneuronal tumor (PGNT) exhibits a characteristic methylation profile and fusions involving PRKCA. In Acta neuropathologica, 137, 837-846. doi:10.1007/s00401-019-01969-2. https://pubmed.ncbi.nlm.nih.gov/30759284/