Disease relevance of LGR4

• Furthermore, the LGR4 null mice showed intrauterine growth retardation as reflected by a 14% decrease in body weight at birth, together with 30% and 40% decreases in kidney and liver weights, respectively [1].
• GPR48 may thus play an important role in invasiveness and metastasis of carcinoma and might therefore represent a potential prognostic marker or therapeutic target [2].
• In contrast, depletion of endogenous GPR48 by RNA interference reduced the invasive potential of HeLa and Lewis lung carcinoma cells not only in vitro but also in vivo [2].
• Moreover, GPR48 expression was significantly associated with lymph node metastasis and inversely correlated with p27 expression in human colon carcinomas [2].

High impact information on LGR4

• Up-regulation of GPR48 induced by down-regulation of p27Kip1 enhances carcinoma cell invasiveness and metastasis [2].
• Forced expression of GPR48 increased both in vitro invasive activity and lung metastasis potency of HCT116 cells [2].
• This amino terminus contains 18 Leu-rich repeats-in contrast with the 3 mammalian glycoprotein hormone receptors and DLGR-1 that contain 9 Leu-rich repeats, but resembling the mammalian LGR-4 and LGR-5 that each have 17 Leu-rich repeats in their amino termini [3].
• LGR4 was widely expressed in kidney, adrenal gland, stomach, intestine, heart, bone/cartilage, and other tissues [1].
• Analysis of the viability of 250 newborn animals suggested a skewed inheritance pattern, indicating that only 40% of the expected LGR4 null mice were born [1].

Biological context of LGR4

• Comparison of overall amino acid sequences indicated that LGR4 and LGR5 are closely related to each other but diverge, during evolution, from the homologous receptor found in snail and the mammalian glycoprotein hormone receptors [4].
• The leucine-rich repeats in LGR4 and LGR5 are arrays of 24 amino acids showing similarity to repeats found in the acid labile subunit of the insulin-like growth factor (IGF)/IGF binding protein complexes as well as slit, decorin, and Toll proteins [4].
• Tissues expressing LGR4 were analyzed based on histochemical staining of the transgene driven by the endogenous LGR4 promoter [1].
• To elucidate the functions of this subgroup of LGRs, LGR4 null mice were generated using a secretory trap approach to delete the majority of the LGR4 gene after the insertion of a beta-galactosidase reporter gene immediately after exon 1 [1].
• We have mapped this receptor to human chromosome 11p14-->p13 by several approaches, including radiation hybrid and interspecific backcross mapping, and show that GPR48 is close to BDNF [5].

Anatomical context of LGR4

• In contrast to the restricted tissue expression of gonadotropin and TSH receptors in gonads and thyroid, respectively, LGR4 is expressed in diverse tissues including ovary, testis, adrenal, placenta, thymus, spinal cord, and thyroid, whereas LGR5 is found in muscle, placenta, spinal cord, and brain [4].
• Northern blot analysis demonstrated high expression of GPR48 in the adult human pancreas, with moderate levels of expression in placenta, kidney, brain, and heart [6].

Associations of LGR4 with chemical compounds

• Phylogenetic analysis showed that there are three LGR subgroups: the known glycoprotein hormone receptors; LGR4 to 6; and a third subgroup represented by LGR7 [7].
• The cellular cyclic AMP level in HEK293 cells was increased following transfection of wild-type GPR48 in a dose-dependent manner [8].

Other interactions of LGR4

• Generation of a constitutively active mutant of human GPR48/LGR4, a G-protein-coupled receptor [8].

References