Leucine-rich repeat-containing G-protein coupled receptors (LGRs) belong to class A G protein-coupled receptors (GPCRs) family. The LGRs have an ancient origin and can be detected in both vertebrates and invertebrates, including the ancestral phylum Cnidaria. Based on their respective phylogenetic placement and the property of their cognate ligands, LGRs can be divided into three types (A, B and C). Type A LGRs are characterized by 7–9 leucine-rich repeats (LRRs) within the LRR domain and a distinctively long hinge region to connect the LRR to the TM domain. Mammalian type A LGRs include the follicle-stimulating hormone receptor (FSHR), thyroid-stimulating hormone receptor (TSHR), and luteinizing hormone receptor (LHR), which can bind their respective glycoprotein hormones to help the receptor activation. Type B LGRs refer to LGR4-6, which were recently deorphanized as the R-spondin receptors. These receptors are evaluated to play roles in stem cell differentiation and association with cancers affecting the gut. Type C LGRs are the third subgroup represented by LGR7 and LGR8, which appeared to correlate with the known reproductive roles and tissue-specific expression of H2 relaxin and insulin-like peptide-3 (INSL3).
Here shows part of LGRs in humans including LGR4, a regulator of cell proliferation, differentiation, and stem cell homeostasis mainly through Wnt/β-catenin signaling; LGR5, a cancer stem cell marker and a downstream target in Wnt/β-catenin signaling; LGR6, a supporter for tumor development and progression through Wnt/β-catenin signaling, and is responsible for fueling the renewal of the sebaceous gland and skin.
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