Pth2r, also known as the parathyroid hormone 2 receptor, is a class B G-protein coupled receptor. It is involved in multiple biological functions, such as regulating calcium transport, nociception mediation, and wound healing. Its endogenous ligand is tuberoinfundibular peptide 39 (TIP39), and the TIP39-Pth2r system is a unique neuropeptide-receptor system in the central nervous system [2,4,5].

In ovarian cancer, Pth2r was found to be highly expressed, and knocking down its expression could inhibit the proliferation, invasion, and migration of tumor cells, suggesting it may serve as a new molecular marker [1]. In lung tissue, the SNP rs13383928 was shown to regulate Pth2r expression, potentially linking it to asbestos-related lung cancer [3]. In zebrafish development, hedgehog (Hh) signaling regulates the expression of pth2r [6]. In chondrocytes, TIP39/Pth2r signaling inhibits proliferation and alters differentiation by modulating Sox9 expression [7].

In conclusion, Pth2r is crucial in various biological processes and disease conditions. Studies in different models, including in cancer and development, have revealed its role in processes like cell proliferation, invasion, and differentiation. Understanding Pth2r's functions may provide insights into disease mechanisms and potential therapeutic targets for diseases such as ovarian and lung cancers [1,3].

References:

1. Xiaowei, Wang, Tong, Lu, Yanjun, Qu, Lili, Fan. 2022. PTH2R is related to cell proliferation and migration in ovarian cancer: a multi-omics analysis of bioinformatics and experiments. In Cancer cell international, 22, 148. doi:10.1186/s12935-022-02566-2. https://pubmed.ncbi.nlm.nih.gov/35410353/

2. Keller, Dávid, Tsuda, Mumeko C, Usdin, Ted B, Dobolyi, Arpád. 2022. Behavioural actions of tuberoinfundibular peptide 39 (parathyroid hormone 2). In Journal of neuroendocrinology, 34, e13130. doi:10.1111/jne.13130. https://pubmed.ncbi.nlm.nih.gov/35499975/

3. Meng, Yuan-Qing, Shi, Qiang, Zhu, Si-Jing, Zhang, Shi-Jiao, Sun, Chang. 2021. Asbestos-Induced Lung Cancer-Associated SNP rs13383928 Regulates PTH2R Expression in Lung Tissue. In Human heredity, , 1-5. doi:10.1159/000513291. https://pubmed.ncbi.nlm.nih.gov/33550301/

4. Dobolyi, Arpád, Palkovits, Miklós, Usdin, Ted B. 2009. The TIP39-PTH2 receptor system: unique peptidergic cell groups in the brainstem and their interactions with central regulatory mechanisms. In Progress in neurobiology, 90, 29-59. doi:10.1016/j.pneurobio.2009.10.017. https://pubmed.ncbi.nlm.nih.gov/19857544/

5. Wang, Xi, Cheng, Xi, Zhao, Lihua, Yang, Dehua, Wang, Ming-Wei. . Molecular insights into differentiated ligand recognition of the human parathyroid hormone receptor 2. In Proceedings of the National Academy of Sciences of the United States of America, 118, . doi:10.1073/pnas.2101279118. https://pubmed.ncbi.nlm.nih.gov/34353904/

6. Bhattacharya, Poulomi, Yan, Yi Lin, Postlethwait, John, Rubin, David A. 2011. Evolution of the vertebrate pth2 (tip39) gene family and the regulation of PTH type 2 receptor (pth2r) and its endogenous ligand pth2 by hedgehog signaling in zebrafish development. In The Journal of endocrinology, 211, 187-200. doi:10.1530/JOE-10-0439. https://pubmed.ncbi.nlm.nih.gov/21880859/

7. Panda, Dibiyendu, Goltzman, David, Jüppner, Harald, Karaplis, Andrew C. 2009. TIP39/parathyroid hormone type 2 receptor signaling is a potent inhibitor of chondrocyte proliferation and differentiation. In American journal of physiology. Endocrinology and metabolism, 297, E1125-36. doi:10.1152/ajpendo.00254.2009. https://pubmed.ncbi.nlm.nih.gov/19706789/