Rgs2, a member of the Regulator of G-protein Signaling (RGS) protein family, is a negative feedback regulator in G Protein-Coupled Receptor (GPCR) signaling. It participates in regulating various cell biological functions by destabilizing the enzyme-substrate complex through the hydrolysis of G Guanosine Triphosphate (GTP), acting as a GTPase activating protein (GAP) [1,2]. Rgs2 can block Gq alpha-mediated signaling and inhibit Gs signaling to certain adenylyl cyclases, thus regulating multiple G-protein linked signaling pathways [2].

Rgs2 has been linked to various diseases. In female common diseases like ovarian cancer, uterine fibroids, and preeclampsia, it is closely associated with their occurrence and development. For example, in human pregnancy, Rgs2 promotes estradiol biosynthesis by trophoblasts, and decreased levels of estradiol are related to preeclampsia [1,3]. In cardiovascular diseases, deregulation of Rgs2 is a crucial factor in the pathogenesis. Rgs2 knockout mice exhibit hypertension phenotype, accelerated cardiac hypertrophy, and heart failure in response to pressure-overload, indicating an inverse correlation between Rgs2 expression and blood pressure, as well as selective down-regulation in cardiac hypertrophy models [4]. In melanoma, Rgs2 over-expression in cell lines inhibits MAPK and AKT activation, preventing cell growth, while Rgs2 knockdown in zebrafish promotes MAPK and AKT activation and ectopic melanocyte differentiation [5]. In castration-resistant prostate cancer, high levels of Rgs2 are associated with poor prognosis, and its expression is increased in this cancer type and enriched under androgen deprivation therapy [6].

In conclusion, Rgs2 is a multifunctional regulator of G-protein signaling, playing essential roles in multiple biological processes and disease conditions. The use of Rgs2 knockout mouse models has significantly contributed to understanding its role in diseases such as cardiovascular diseases and prostate cancer, providing potential therapeutic targets and biomarkers for these diseases.

References:

1. Xu, Qiang, Yao, Mukun, Tang, Chao. 2023. RGS2 and female common diseases: a guard of women's health. In Journal of translational medicine, 21, 583. doi:10.1186/s12967-023-04462-3. https://pubmed.ncbi.nlm.nih.gov/37649067/

2. Kehrl, John H, Sinnarajah, Srikumar. . RGS2: a multifunctional regulator of G-protein signaling. In The international journal of biochemistry & cell biology, 34, 432-8. doi:. https://pubmed.ncbi.nlm.nih.gov/11906816/

3. Tang, Chao, Jin, Meiyuan, Ma, Bingbing, Li, Jiayong, Xu, Qiang. 2023. RGS2 promotes estradiol biosynthesis by trophoblasts during human pregnancy. In Experimental & molecular medicine, 55, 240-252. doi:10.1038/s12276-023-00927-z. https://pubmed.ncbi.nlm.nih.gov/36653442/

4. Tsang, Sharon, Woo, Anthony Yiu-Ho, Zhu, Weizhong, Xiao, Rui-Ping. 2010. Deregulation of RGS2 in cardiovascular diseases. In Frontiers in bioscience (Scholar edition), 2, 547-57. doi:. https://pubmed.ncbi.nlm.nih.gov/20036967/

5. Lin, Sheng-Jia, Huang, Yin-Cheng, Chen, Hao-Yuan, Liu, Yu-Chien, Cheng, Yi-Chuan. . RGS2 Suppresses Melanoma Growth via Inhibiting MAPK and AKT Signaling Pathways. In Anticancer research, 41, 6135-6145. doi:10.21873/anticanres.15433. https://pubmed.ncbi.nlm.nih.gov/34848468/

6. Linder, Anna, Larsson, Karin, Welén, Karin, Damber, Jan-Erik. 2020. RGS2 is prognostic for development of castration resistance and cancer-specific survival in castration-resistant prostate cancer. In The Prostate, 80, 799-810. doi:10.1002/pros.23994. https://pubmed.ncbi.nlm.nih.gov/32449815/