Prokr1, short for Prokineticin receptor 1, is a G protein-coupled receptor. It is involved in various metabolic functions, such as regulating muscle fiber composition, insulin sensitivity, and energy metabolism. It is part of signaling pathways like the Gs-mediated phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) and Gq-mediated PI3K/AKT and MAPK/ERK signaling pathways [1,2]. Genetic models, like knockout (KO) mouse models, are crucial for studying its functions.

In Prokr1-deficient mice, unfavorable metabolic phenotypes were observed, including lower lean mass, enlarged muscle fibers, impaired glucose and insulin tolerance, reduced energy expenditure, and exercise performance. The deletion of Prokr1 led to decreased oxidative muscle fiber composition and reduced activity in the Prokr1-CREB-Nr4a2 pathway, which could be restored by AAV-mediated Prokr1 rescue [1]. Additionally, mRNA and protein levels of Prokr1 were significantly decreased in the skeletal muscle and white adipose tissue of diet-induced obese mice [2].

In conclusion, Prokr1 plays essential roles in metabolic functions, especially in regulating muscle fiber composition and insulin sensitivity. The study of Prokr1 KO mouse models has revealed its significance in metabolic-related diseases, highlighting its potential as a therapeutic target for treating conditions such as metabolic disorders and insulin resistance [1,2].

References:

1. Mok, Jongsoo, Park, Jeong Hwan, Yeom, Su Chong, Park, Joonghoon. 2024. PROKR1-CREB-NR4A2 axis for oxidative muscle fiber specification and improvement of metabolic function. In Proceedings of the National Academy of Sciences of the United States of America, 121, e2308960121. doi:10.1073/pnas.2308960121. https://pubmed.ncbi.nlm.nih.gov/38232288/

2. Mok, Jongsoo, Park, Tae Sub, Kim, Sunhong, Choi, Cheol Soo, Park, Joonghoon. 2020. Prokineticin receptor 1 ameliorates insulin resistance in skeletal muscle. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 35, e21179. doi:10.1096/fj.202001641R. https://pubmed.ncbi.nlm.nih.gov/33184929/