ライフサイエンスコーパス: GPR54

1 nder the association of Galpha subunits with GPR54.

2 roperties, or protein interaction network of GPR54.

3 le of inducing an LH surge in the absence of GPR54.

4 pocampal neurons, which are known to express GPR54.

5 Mutations in GPR54, a G protein-coupled receptor gene, cause autosoma

6 s1 gene codes for kisspeptin, which binds to GPR54, a G-protein-coupled receptor.

7 Here, we reveal that GPR54 activation by its natural ligand Kisspeptin-10 (Kp

8 Kiss1, Gpr54 and Dusp18 knockout mice all exhibit osteoclast hy

9 cociously, and we describe the expression of GPR54 and KiSS-1 in the hypothalamus during the peripube

10 ree were homozygous for an L148S mutation in GPR54, and an unrelated proband with idiopathic hypogona

11 The peptide and its receptor GPR54 are abundant in the hypothalamus and have been imp

12 Kisspeptin and GPR54 are expressed in discrete regions of the forebrain

13 Kisspeptin and its cognate receptor, GPR54, are critical for reproductive development and for

14 lated by neuronal activity and activation of GPR54 by kisspeptin may in turn contribute to sustain ba

15 We showed previously that the activation of GPR54 by kisspeptin-10 suppressed CXCR4-mediated chemota

16 that the activation of its cognate receptor GPR54 by kisspeptin-10 suppressed the capacity of the pr

17 Activation of the G-protein-coupled receptor GPR54 by kisspeptins during normal puberty promotes the

18 Activation of KISS1 receptor (KISS1R or GPR54) by its ligands (Kisspeptins) regulates a diverse

19 We demonstrate here that activation of GPR54 can also abolish the activation of Akt by the tyro

20 RH) secretion, and mutations or deletions of GPR54 cause hypogonadotropic hypogonadism in humans and

21 S) in the second intracellular loop (IL2) of GPR54 causes idiopathic hypogonadotropic hypogonadism, a

22 Deletion of Gpr54 decreases Bmp7 expression and Smad1 phosphorylatio

23 The Gpr54-deficient mice had isolated hypogonadotropic hypog

24 In parallel, a Gpr54-deficient mouse model was created and phenotyped.

25 Here we report that Gpr54 deletion leads to kidney branching morphogenesis a

26 itative PCR data showing kisspeptin receptor GPR54 expression in the arcuate nucleus, and the attenua

27 In contrast, diverse GPR54 functional responses are markedly inhibited by the

28 y, we used female mice with deletions in the GPR54 gene [GPR54 knock-outs (KOs)] to test the hypothes

29 ome (KS), whereas mutations in the GNRHR and GPR54 genes cause idiopathic hypogonadotropic hypogonadi

30 (e.g. Rgs2, Rgs4, Rgs5, Rgs16, Gpr23, Gpr30, Gpr54, Gpr64, and Gna13).

31 ptin fibers, express the kisspeptin receptor GPR54 in the preoptic region, but not in the tuberal reg

32 Gpr54 inactivation results in a high risk of low glomeru

33 We show here that the activation of GPR54 induced immediate and profound changes of cell mor

34 We also demonstrated that activation of GPR54 inhibited Akt phosphorylation after the activation

35 GPR54 is a G-protein-coupled receptor, which binds kissp

36 Therefore, Kp-10/Gpr54 is a promising therapeutic target to abrogate bone

37 Interestingly, GPR54 is also highly expressed in granule cells of the h

38 The G-protein-coupled receptor (GPCR) GPR54 is essential for the development and maintenance o

39 Gpr54 is expressed in condensed mesenchyme at E12.5 and

40 However, whether Gpr54 is involved in embryonic kidney development and ho

41 However, GPR54 is necessary for proper male-like development of s

42 t study examined how expression of KiSS1 and GPR54 is regulated in rat hippocampus, using in vivo and

43 metastasis suppressor KiSS1 and its receptor GPR54 is still incompletely characterized.

44 the cognate ligand for the metastin receptor GPR54, is a peptide known to dramatically reduce metasta

45 G-protein-coupled receptor 54 (Gpr54, KISS1 receptor) plays critical roles in puberty r

46 heral or central administration in Kiss1- or Gpr54 (Kiss1r)-null mutant mice.

47 and its cognate G protein-coupled receptor, GPR54 (kisspeptin receptor, Kiss-R), are critical for th

48 Using adult wild-type (WT) and GPR54 knock-out (KO) mice, we first tested whether kissp

49 emale mice with deletions in the GPR54 gene [GPR54 knock-outs (KOs)] to test the hypothesis that kiss

50 e found that hormone-replaced gonadectomized GPR54 KO males and females displayed appropriate gender-

51 Interestingly, adult testosterone-treated GPR54 KO males displayed "female-like" numbers of tyrosi

52 es, whereas similarly treated WT females and GPR54 KO males showed no preference for either sex.

53 As predicted, we found that GPR54 KO mice do not exhibit a postovariectomy rise in L

54 onic GnRH/LH secretion would be disrupted in GPR54 KOs and that such animals would be incapable of sh

55 ns and produced a GnRH-dependent LH surge in GPR54 KOs.

56 on the antimetastatic function of KiSS1 and GPR54 largely focused on the autocrine inhibition of cel

57 We show that Kp-10 binding to Gpr54 leads to the up-regulation of Dusp18.

58 Among others, the GPR54-ligand KISS1 was identified as a direct transcript

59 The activation of ROCK also contributed to GPR54-mediated apoptosis in 293 cells, and its effect wa

60 n histochemistry indicated robust KiSS-1 and GPR54 mRNA expression in the region of the arcuate nucle

61 n intact females, but not in agonadal males, GPR54 mRNA levels in the hypothalamus increased approxim

62 GPR54 mRNA, on the other hand, was reduced by 20-30% at

63 increased plasma LH levels in both Kiss1 and Gpr54 mutant male mice similar to the responses in wild-

64 pathic hypogonadotropic hypogonadism without GPR54 mutations.

65 kisspeptin receptor (KISS1R, formerly called GPR54), neurokinin B (TAC3), and the neurokinin B recept

66 Using a transgenic Gpr54-null IRES-LacZ knock-in mouse model, we demonstrat

67 ates a receptor coupled to Galphaq subunits (GPR54 or KiSS-1R).

68 The G protein-coupled kisspeptin receptor (GPR54 or KISS1R) is an important mediator in reproductio

69 us ligand for the G-protein-coupled receptor GPR54 (or AXOR12, or OT7T175).

70 e interaction of kisspeptin and its receptor GPR54 plays a crucial role in governing the onset of pub

71 ne metastasis suppression effect of KiSS1 on GPR54-positive tumor cells.

72 ns and mice, a loss of function mutations of GPR54 prevents the onset of puberty and leads to hypogon

73 isualized the expression and localization of GPR54 receptors in human cells and in whole mouse pancre

74 Mechanistically, Gpr54 recruits both active Src and the Dusp18 phosphatas

75 Together, these data suggest that Gpr54 regulates Bmp7 expression through NFAT2 and Sp1 an

76 n and luciferase assays, we demonstrate that Gpr54 regulates NFAT2- and Sp1-mediated Bmp7 transcripti

77 Activation of GPR54 resulted in the ERK-dependent expression of tumor

78 ings are consistent with the hypothesis that GPR54 signaling by its cognate ligand in the primate hyp

79 Kisspeptin-GPR54 signaling has been implicated in the regulation of

80 discusses the latest ideas about kisspeptin-GPR54 signaling in the neuroendocrine regulation of repr

81 To further study the role of GPR54 signaling in the onset of primate puberty, we used

82 nts; however, the precise role of kisspeptin-GPR54 signaling in the regulation of gonadotropin secret

83 We also postulated that kisspeptin-GPR54 signaling is critical for the generation of the es

84 evelopment by androgens, we assessed whether GPR54 signaling is essential for sexual differentiation

85 KO) mice, we first tested whether kisspeptin-GPR54 signaling is necessary for male and female sexual

86 Our findings indicate that kisspeptin-GPR54 signaling is not required for male or female copul

87 Next, we examined whether GPR54 signaling is required for proper display of olfact

88 Thus, in mice, kisspeptin-GPR54 signaling is required for the tonic stimulation of

89 nduced by SDF-1 indicates that activation of GPR54 signaling may negatively regulate the role of CXCR

90 KOs)] to test the hypothesis that kisspeptin-GPR54 signaling provides the drive necessary for tonic G

91 Other reproductive roles for kisspeptin-GPR54 signaling, including the regulation of development

92 on is disrupted in the absence of kisspeptin-GPR54 signaling.

93 also been shown in cells that do not express GPR54, suggesting a paracrine mechanism in which kisspep

94 ecapitulates the effects observed with L148S GPR54, suggesting the critical importance of this hydrop

95 GnRH neurons express the kisspeptin receptor GPR54 upon circuit formation, suggesting that the signal

96 Activation of GPR54 was shown to inhibit cell motility and invasion of

97 The signaling of GPR54 was sufficient to trigger apoptosis in epithelial

98 nal differences between wild-type and mutant GPR54 were examined in vitro.

99 examined for mutations in a candidate gene, GPR54, which encodes a G protein-coupled receptor.

100 the kisspeptins, and their cognate receptor, GPR54, which have been implicated in the regulation of G