ライフサイエンスコーパス: GRK4

1 s explaining the generally low expression of GRK4.

2 that human retina expressed all GRKs except GRK4.

3 46 codons in the carboxyl-terminal domain of GRK4.

4 f the three GRK subgroups (GRK1, GRK2/3, and GRK4/5/6) shares even a single intron in common, indicat

5 duced receptor phosphorylation by 77%, while GRK4-6-specific mAbs have no effect.

6 GRK4 A486V transgenic mice, inducible cardiomyocyte-spec

7 ession of human GRK4 wild type (WT) or human GRK4 A486V variant had increased cardiac infarction, exa

8 of cardiac function in patients carrying the GRK4 A486V variant than in WT carriers.

9 In an analysis of how GRK4 affects the developing kidney, the authors found th

10 activity is dispensable because kinase-dead GRK4 (altered GRK4 that cannot result in phosphorylation

11 In contrast, overexpression of GRK4 and -6 led mainly to agonist-independent phosphoryl

12 ect of GRK4 variants on the functionality of GRK4 and GRK4's actions in cellular signaling during kid

13 Interestingly, similar regions in GRK4 and GRK6 appear to be palmitoylated (and involved i

14 For example, two members of this family, GRK4 and GRK6, contain C-terminal cysteine residues that

15 Three novel genes-SLC39A8, GRK4 and HGFAC-within loci associated with altered alcoh

16 Coexpression of GRK4 and the D1 receptor in a heterologous system induce

17 ll evidence were GAD1, NTRK3, ADRA2A, FZD10, GRK4, and SLC6A4.

18 -activated D1R is regulated by both SNX5 and GRK4, and that SNX5 is critical to the recycling of the

19 These findings identify GRK4 as novel regulator of cilia and of kidney developme

20 major type of tubule cell death mediated by GRK4, because GRK4 significantly increased receptor inte

21 and activator of transcription (STAT)1 as a GRK4 binding protein, which co-localized with GRK4 in th

22 vity of G protein-coupled receptor kinase 4 (GRK4), caused by increased expression or genetic variant

23 through G-protein-coupled receptor kinase 4 (GRK4), comparatively little is known about other aspects

24 n this article, we present data showing that GRK4 constitutively phosphorylates the D1 receptor in th

25 lation resulting from mutationally activated GRK4 contributes to the heritable component of human ess

26 , whereas kidney tubule-specific knockout of GRK4 decreased injury-induced kidney dysfunction.

27 Moreover, GRK4 depletion in zebrafish and cellular mammalian model

28 Zebrafish depleted of Grk4 develop impaired glomerular filtration, generalized

29 least, the G protein-coupled receptor kinase GRK4 does not display a preference for the agonist-occup

30 RK2-6) expressed in kidneys, the increase in GRK4 expression was much more apparent than that of the

31 SiRNA-mediated downregulation of GRK4 expression, recovered the impaired inhibitory effec

32 In vivo downregulation of renal GRK4 expression, via ultrasound-targeted microbubble des

33 Hypertension-associated genetic variants of GRK4 fail to rescue any of the observed phenotypes, sugg

34 nd it is also unclear whether or how altered GRK4 function might affect kidney development.

35 The genomic organization of the GRK4 gene is completely distinct from that of the human

36 The human GRK4 gene is composed of 16 exons extending over 75 kilo

37 istinguishes the betaARK (GRK2 and GRK3) and GRK4 (GRK4, GRK5, and GRK6) subfamilies.

38 uishes the betaARK (GRK2 and GRK3) and GRK4 (GRK4, GRK5, and GRK6) subfamilies.

39 erved between members of the GRK4 subfamily (GRK4, GRK5, and GRK6).

40 in binding sites, and is highly conserved in GRK4, GRK5, and GRK6.

41 bind PIP2, betaARK (GRK2), betaARK2 (GRK3), GRK4, GRK5, and GRK6.

42 pecifically react with GRK2 and GRK3 or with GRK4, GRK5, and GRK6.

43 G protein-coupled receptor kinase 4 (GRK4) has been reported to play an important role in hyp

44 conservation, whereas GRK1 and particularly GRK4 have accumulated amino acid changes at extremely ra

45 Several nonsynonymous genetic variants of GRK4 have been only partially linked to hypertension, al

46 Loss of GRK4 in embryonic zebrafish causes kidney dysfunction an

47 d the expression and distribution pattern of GRK4 in mouse heart after MI.

48 ation and co-immunoprecipitation of ETBR and GRK4 in renal proximal tubule (RPT) cells from both WKY

49 The mRNA and protein levels of GRK4 in the heart were increased after MI.

50 RK4 binding protein, which co-localized with GRK4 in the nuclei of renal tubule cells.

51 l of present study is to explore the role of GRK4 in the pathogenesis and progression of MI.

52 GRK4 increases cardiomyocyte injury during MI by inhibit

53 HDAC4 S632A mutation partially restored the GRK4-induced inhibition of autophagy.

54 d beta2-adrenergic receptor, indicating that GRK4 is a functional protein kinase.

55 GRK4 is capable of augmenting the desensitization of the

56 GRK4 is implicated in the regulation of blood pressure,

57 amily (GRKs 4, 5, and 6) suggests that mouse GRK4 is not alternatively spliced in a manner analogous

58 G protein-coupled receptor kinase 4 (GRK4) is considered a central regulator of blood pressur

59 fibroblasts and in a kidney spheroid model, GRK4 knockdown produced elongated primary cilia.

60 genic mice, inducible cardiomyocyte-specific GRK4 knockout mice, were generated and subjected to MI w

61 g were ameliorated in cardiomyocyte-specific GRK4 knockout mice.

62 mice, while no differences were detected for Grk4 KO mice in alcohol or nicotine consumption and pref

63 In addition, studies elucidating how GRK4 may modulate cellular signaling are sparse.

64 whose inactive mutation effectively reversed GRK4-mediated RIPK1 activation and tubule cell death.

65 he developing kidney, the authors found that GRK4 modulates mammalian target of rapamycin (mTOR) sign

66 Thus, the GRK4 mRNA and the GRK4 protein can exist as four distinc

67 Human GRK4 mRNA is expressed highly only in testis, and both a

68 regions undergo alternative splicing in the GRK4 mRNA, resulting from the presence or absence of exo

69 Little is known about the effects of GRK4 on cellular signaling, and it is also unclear wheth

70 d loss-of-function experiments revealed that GRK4 overexpression exacerbated acute kidney ischemia/re

71 GRK4 overexpression in cardiomyocytes aggravated apoptos

72 Reconstitution with human wild-type GRK4 partially rescues these phenotypes.

73 Additionally, GRK4 phosphorylated STAT1 at serine 727, whose inactive

74 G protein-coupled receptor kinase 4 (GRK4) plays a vital role in essential hypertension and m

75 the regulation of blood pressure, and three GRK4 polymorphisms (R65L, A142V, and A486V) are associat

76 Thus, the GRK4 mRNA and the GRK4 protein can exist as four distinct variant forms.

77 The four GRK4 proteins have been expressed, and all incorporate [

78 G protein-coupled receptor kinase 4 (GRK4) regulates renal sodium and water reabsorption.

79 K4 variants on the functionality of GRK4 and GRK4's actions in cellular signaling during kidney devel

80 lia and of kidney development independent of GRK4's kinase function and provide evidence that the GRK

81 tubule cell death mediated by GRK4, because GRK4 significantly increased receptor interacting kinase

82 Kidney-targeted GRK4 silencing with nanoparticle delivery considerably a

83 , is highly conserved between members of the GRK4 subfamily (GRK4, GRK5, and GRK6).

84 Examination of the mouse GRK4 subfamily (GRKs 4, 5, and 6) suggests that mouse GR

85 Indeed, all the members of the GRK4 subfamily exhibit PIP2-dependent receptor kinase ac

86 GRK6 is a member of the GRK4 subfamily of GRKs, which is represented in most, if

87 and 6 genes reveals that all members of the GRK4 subfamily share an identical gene structure, in whi

88 structure, not structurally observed for the GRK4 subfamily, most likely occurs through the release o

89 ispensable because kinase-dead GRK4 (altered GRK4 that cannot result in phosphorylation of the target

90 mediated exclusively by the alpha isoform of GRK4; the beta, gamma, and delta isoforms are ineffectiv

91 de polymorphisms in several genes, including GRK4, TRAIP, and RNF123, indicating that depression may

92 Thus, our findings reveal that GRK4 triggers necroptosis and aggravates kidney ischemia

93 inase function and provide evidence that the GRK4 variants believed to act as hyperactive kinases are

94 ver, some evidence suggests that function of GRK4 variants may involve more than regulation of dopami

95 nts suggest that hypertension in carriers of GRK4 variants may not be explained solely by kinase hype

96 To better understand the effect of GRK4 variants on the functionality of GRK4 and GRK4's ac

97 Although GRK4 variants with elevated kinase activity have been as

98 This study provides a mechanism by which GRK4, via regulation of renal ETBR function, participate

99 pliced in a manner analogous to human or rat GRK4, whereas GRK6 undergoes extensive alternative splic

100 MI also induced the nuclear translocation of GRK4, which inhibited autophagy by increasing HDAC4 phos

101 sgenic mice with the overexpression of human GRK4 wild type (WT) or human GRK4 A486V variant had incr

102 a system incorporating constitutively active GRK4 will be prone to dysregulation, perhaps explaining

103 arison of the deduced amino acid sequence of GRK4 with those of the closely related GRK5 and GRK6 sug

104 sion of G-protein-coupled receptor kinase 4 (GRK4) with wild type receptor resulted in an increase in