Progestin and adipoQ receptor family member 8 (PAQR8)

Progestin and adipoQ receptor family member 8 (PAQR8), also known as membrane progesterone receptor beta (mPRβ), is a member of the PAQR family of membrane receptors. Unlike classical nuclear progesterone receptors, PAQR8 acts at the cell membrane to mediate rapid, non-genomic effects of progesterone and potentially other progestins. It differs from canonical G protein-coupled receptors by having only six transmembrane domains and does not utilize typical GPCR signaling; instead, it activates intracellular pathways such as ERK/MAPK and PI3K in response to progesterone. PAQR8 is highly expressed in nervous tissue, where it has demonstrated roles in neurite outgrowth, neuroprotection, and possibly reproductive regulation. Its physiological and pathophysiological roles are being investigated, especially in the context of neural function and potentially reproductive or neuroendocrine disease, but it is not yet a validated therapeutic target in clinical use[2][3][4][5][6].

Other names

Membrane progesterone receptor betaMPRBC6orf33LMPB1mPR betamembrane progestin receptor betalysosomal membrane protein in brain 1membrane progesterone receptor betaprogestin and adipoQ receptor family member VIIIPAQR8

Activation by progesterone leads to stimulation of ERK phosphorylation via MAPK cascade, independently of traditional G protein-coupled receptor (GPCR) signaling[3][4][6] Promotes neurite outgrowth via PI3K-Rac1-MAPK cascade in neuronal cells[3][4] Does not signal via canonical G-protein (Gs, Gi/o, Gq) pathways[3][4]