Ptpn21, a protein tyrosine phosphatase, plays diverse roles in multiple biological processes. It is involved in regulating hematopoietic stem cell (HSC) homeostasis and biomechanics, and is associated with pathways such as neuroactive ligand-receptor interaction, EGFR/PI3K/AKT, and MAPK signaling pathways [1,2,3,6]. Ptpn21 is of great biological importance as it impacts cellular functions like cell mobility, quiescence, apoptosis, and differentiation, and is also related to cancer development, inflammation, and fibrosis [1-6,8-10]. Genetic models, including knockout models, are valuable for studying its functions.

In a Ptpn21-knockout (KO) mouse model, deletion of Ptpn21 led to HSC egress from the niche, enhanced HSC mobility, decreased quiescence, increased apoptosis, and defective reconstitution capacity. Ptpn21 deletion also decreased HSC stiffness and increased physical deformability by dephosphorylating Spetin1, which impaired cytoskeletal remodeling [1]. In glioma, silencing of Ptpn21 produced anticancer effects by restraining the EGFR/PI3K/AKT pathway [3]. In acute lymphoblastic leukemia cells, knocking out the PTPN21-CDSlong isoform increased sensitivity to NK-mediated killing [4]. In experimental pulmonary fibrosis, loss of Ptpn21 in epithelial cells disrupted mitochondrial metabolic homeostasis and aggravated fibrosis [5].

In conclusion, Ptpn21 is essential for maintaining cellular mechanics in HSCs, as well as for various cellular functions in different tissues. The KO/CKO mouse models have revealed its significance in diseases such as hematopoietic disorders, cancer, and pulmonary fibrosis, contributing to a better understanding of disease mechanisms and potentially providing new targets for treatment.

References:

1. Ni, Fang, Yu, Wen-Mei, Wang, Xinyi, Scadden, David T, Qu, Cheng-Kui. 2019. Ptpn21 Controls Hematopoietic Stem Cell Homeostasis and Biomechanics. In Cell stem cell, 24, 608-620.e6. doi:10.1016/j.stem.2019.02.009. https://pubmed.ncbi.nlm.nih.gov/30880025/

2. Yang, YanE, Yang, WenChao, Su, Xingxing, Cheng, CaiXia. 2023. Prognostic value and immunological role of PTPN21 in pan-cancer analysis. In Central-European journal of immunology, 48, 111-125. doi:10.5114/ceji.2023.129970. https://pubmed.ncbi.nlm.nih.gov/37692032/

3. Li, Xiao-Qiang, Liu, Bo-Chuan, Jiang, Xiao-Bing, Zhao, Hai-Kang, Zhang, Liang. 2022. Inhibition of PTPN21 has antitumor effects in glioma by restraining the EGFR/PI3K/AKT pathway. In Toxicology and applied pharmacology, 451, 116180. doi:10.1016/j.taap.2022.116180. https://pubmed.ncbi.nlm.nih.gov/35907586/

4. Wang, Huafang, Zhu, Ni, Ye, Xiaohang, Xiao, Haowen, Huang, He. 2020. PTPN21-CDSlong isoform inhibits the response of acute lymphoblastic leukemia cells to NK-mediated lysis via the KIR/HLA-I axis. In Journal of cellular biochemistry, 121, 3298-3312. doi:10.1002/jcb.29601. https://pubmed.ncbi.nlm.nih.gov/31898344/

5. Lian, Hui, Xu, Kai, Chang, Airu, Wang, Lan, Yu, Guoying. 2024. Loss of PTPN21 disrupted mitochondrial metabolic homeostasis and aggravated experimental pulmonary fibrosis. In Respiratory research, 25, 426. doi:10.1186/s12931-024-03041-4. https://pubmed.ncbi.nlm.nih.gov/39633451/

6. Zhu, Ni, Wei, Jieping, Wang, Li-Mengmeng, Huang, He, Xiao, Haowen. 2024. Overexpression of PTPN21 promotes proliferation of EGF-stimulated acute lymphoblastic leukemia cells via the MAPK signaling pathways. In Hematology (Amsterdam, Netherlands), 29, 2356292. doi:10.1080/16078454.2024.2356292. https://pubmed.ncbi.nlm.nih.gov/38785187/