Map2k3, also known as Mitogen-Activated Protein Kinase Kinase 3, is a crucial component in multiple signaling pathways. It is involved in the regulation of cell proliferation, invasion, and immune-related processes [2,3,4]. For instance, it participates in the p38-transforming growth factor-β signaling pathway, which has implications for cardiac remodeling and fibrosis [1].

In a study on hypertensive heart disease, cardiac fibroblast-specific deletion of activating transcription factor 3 (ATF3KO) led to exaggerated ventricular remodeling, a phenotype rescued by genetic Map2k3 knockdown. This indicates that Map2k3 mediates the profibrotic/hypertrophic effects in ATF3KO animals, suggesting its role in hypertensive cardiac remodeling [1]. In esophageal squamous cell carcinoma (ESCC), Map2k3 inhibited cell proliferation and invasion, and its down-regulation correlated with poor survival. Exosomal miR-19b-3p from ESCC patients could suppress Map2k3 expression to promote tumorigenesis [2].

In summary, Map2k3 plays essential roles in diverse biological processes and disease conditions. The use of gene knockout models, such as the ATF3KO in cardiac fibroblasts, has been instrumental in revealing its role in hypertensive cardiac remodeling. In cancer, like ESCC, its function in inhibiting tumorigenesis is emerging, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Li, Yulin, Li, Zhenya, Zhang, Congcong, Ma, Xin-Liang, Du, Jie. 2017. Cardiac Fibroblast-Specific Activating Transcription Factor 3 Protects Against Heart Failure by Suppressing MAP2K3-p38 Signaling. In Circulation, 135, 2041-2057. doi:10.1161/CIRCULATIONAHA.116.024599. https://pubmed.ncbi.nlm.nih.gov/28249877/

2. Zhang, Ying, Lu, Weiqing, Chen, Yelong, Wang, Hu, Liu, Zhaoyong. 2021. The miR-19b-3p-MAP2K3-STAT3 feedback loop regulates cell proliferation and invasion in esophageal squamous cell carcinoma. In Molecular oncology, 15, 1566-1583. doi:10.1002/1878-0261.12934. https://pubmed.ncbi.nlm.nih.gov/33660414/

3. Pu, Bei, Feng, Shi, Gu, Lijuan, Xiong, Xiaoxing, Wei, Liang. 2024. Exploring MAP2K3 as a prognostic biomarker and potential immunotherapy target in glioma treatment. In Frontiers in neurology, 15, 1387743. doi:10.3389/fneur.2024.1387743. https://pubmed.ncbi.nlm.nih.gov/38938778/

4. Gu, Kefei, Wang, Tan, Peng, Liying, Zhao, Yueliang. 2022. FIP-fve Stimulates Cell Proliferation and Enhances IL-2 Release by Activating MAP2K3/p38α (MAPK14) Signaling Pathway in Jurkat E6-1 Cells. In Frontiers in nutrition, 9, 881924. doi:10.3389/fnut.2022.881924. https://pubmed.ncbi.nlm.nih.gov/35614983/