Foundation for Applied Molecular Evolution, P.O. Box 13174, Gainesville, FL 32604, USA.
Biochem Soc Trans. 2012 Feb;40(1):200-4. doi: 10.1042/BST20110638.
The steroid hormone progesterone regulates many critical aspects of vertebrate physiology. The nuclear receptor for progesterone functions as a ligand-activated transcription factor, directly regulating gene expression. This type of signalling is referred to as the 'genomic' pathway. Nevertheless, progesterone also stimulates rapid physiological effects that are independent of transcription. This pathway, termed 'non-genomic', is mediated by the mPRs (membrane progesterone receptors). These mPRs belong to a larger class of membrane receptors called PAQRs (progestin and adipoQ receptors), which include receptors for adiponectin in vertebrates and osmotin in fungi. mPRs have been shown to activate inhibitory G-proteins, suggesting that they act as GPCRs (G-protein-coupled receptors). However, PAQRs do not resemble GPCRs with respect to topology or conserved sequence motifs. Instead, they more closely resemble proteins in the alkaline ceramidase family and they may possess enzymatic activity. In the present paper, we highlight the evidence in support of each model and what is currently known for PAQR signal transduction of this non-canonical receptor.
甾体激素孕酮调节脊椎动物生理学的许多关键方面。孕酮的核受体作为配体激活转录因子，直接调节基因表达。这种信号转导方式被称为“基因组”途径。然而，孕酮还能刺激快速的生理效应，而这些效应不依赖于转录。这种途径，称为“非基因组”，由 mPR（膜孕酮受体）介导。这些 mPR 属于更大的一类膜受体，称为 PAQR（孕激素和脂联素 Q 受体），包括脊椎动物中脂联素的受体和真菌中的 osmotin 的受体。已经表明 mPR 可激活抑制性 G 蛋白，表明它们作为 G 蛋白偶联受体（GPCR）起作用。然而，PAQR 在拓扑结构或保守序列基序方面与 GPCR 不相似。相反，它们更类似于碱性 ceramidase 家族的蛋白质，并且它们可能具有酶活性。在本文中，我们强调了支持每种模型的证据，以及目前已知的这种非典型受体的 PAQR 信号转导。
