Prkcd-KO Mouse

Prkcd, also known as Protein kinase C delta, is a member of the PKC family. It has diverse biological properties and is involved in multiple biological processes. It plays a role in B and T cell activation, cytokine production, and is associated with pathways related to immune tolerance, apoptosis, mitochondrial function, and mitophagy [2,3,6,7].

In disease-related studies, Prkcd deficiency has been identified as a monogenic cause of systemic lupus erythematosus, and patients with such deficiency also present with autoimmune lymphoproliferative syndrome-related syndromes and infection susceptibility [2,7,8]. In chronic obstructive pulmonary disease (COPD), Prkcd contributes to disease development by promoting inflammatory response, apoptosis, mitochondrial dysfunction, and MUC5AC hypersecretion, suggesting it could be a potential therapeutic target [1]. In gastric cancer, TRIM69 suppresses anoikis resistance and metastasis through ubiquitin-proteasome-mediated degradation of Prkcd [4]. In triple-negative breast cancer (TNBC), PRKCD_pY313 activates Src and p38 MAPK to promote TNBC progression [5]. In Vogt-Koyanagi-Harada disease, certain polymorphisms of Prkcd are associated with disease susceptibility [6].

In conclusion, Prkcd is crucial in immune-related biological processes and is significantly associated with multiple diseases, including autoimmune diseases, COPD, gastric cancer, TNBC, and Vogt-Koyanagi-Harada disease. Research on Prkcd, especially through genetic models, helps to understand the disease mechanisms and may provide new therapeutic targets.

References:

1. Li, Siqi, Huang, Qiong, Zhou, Dongbo, He, Baimei. 2022. PRKCD as a potential therapeutic target for chronic obstructive pulmonary disease. In International immunopharmacology, 113, 109374. doi:10.1016/j.intimp.2022.109374. https://pubmed.ncbi.nlm.nih.gov/36279664/

2. Jefferson, Lucy, Ramanan, Athimalaipet Vaidyanathan, Jolles, Stephen, Belot, Alexandre, Roderick, Marion Ruth. 2023. Phenotypic Variability in PRKCD: a Review of the Literature. In Journal of clinical immunology, 43, 1692-1705. doi:10.1007/s10875-023-01579-4. https://pubmed.ncbi.nlm.nih.gov/37794137/

3. Munson, Michael J, Mathai, Benan J, Ng, Matthew Yoke Wui, Fang, Evandro F, Simonsen, Anne. 2021. GAK and PRKCD are positive regulators of PRKN-independent mitophagy. In Nature communications, 12, 6101. doi:10.1038/s41467-021-26331-7. https://pubmed.ncbi.nlm.nih.gov/34671015/

4. Sun, Linqing, Chen, Yuqi, Xia, Lu, Shi, Tongguo, Chen, Weichang. 2023. TRIM69 suppressed the anoikis resistance and metastasis of gastric cancer through ubiquitin‒proteasome-mediated degradation of PRKCD. In Oncogene, 42, 3619-3632. doi:10.1038/s41388-023-02873-6. https://pubmed.ncbi.nlm.nih.gov/37864033/

5. Deng, Yujiao, Hou, Zhanwu, Li, Yizhen, Liu, Huadong, Dai, Zhijun. 2024. Superbinder based phosphoproteomic landscape revealed PRKCD_pY313 mediates the activation of Src and p38 MAPK to promote TNBC progression. In Cell communication and signaling : CCS, 22, 115. doi:10.1186/s12964-024-01487-z. https://pubmed.ncbi.nlm.nih.gov/38347536/

6. Zhou, Chunya, Cai, Shiya, Xie, Yuhong, Yang, Peizeng, Hu, Jianmin. 2023. Genetic association of PRKCD and CARD9 polymorphisms with Vogt-Koyanagi-Harada disease in the Chinese Han population. In Human genomics, 17, 9. doi:10.1186/s40246-023-00459-7. https://pubmed.ncbi.nlm.nih.gov/36782298/

7. Lo, Mindy S. . Monogenic Lupus. In Current rheumatology reports, 18, 71. doi:10.1007/s11926-016-0621-9. https://pubmed.ncbi.nlm.nih.gov/27812953/

8. Roderick, Marion R, Jefferson, Lucy, Renton, William, Belot, Alexandre. 2023. Compound Heterozygous Mutations in PRKCD Associated with Early-Onset Lupus and Severe and Invasive Infections in Siblings. In Journal of clinical immunology, 43, 703-705. doi:10.1007/s10875-022-01416-0. https://pubmed.ncbi.nlm.nih.gov/36650346/