ライフサイエンスコーパス: GRK3

1 ine 379, which was predominantly mediated by GRK3.

2 phosphorylation of serine 369 within KOR by GRK3.

3 nated with coexpression of Galpha(tr) or MAS-GRK3.

4 to that induced by wild type beta-arrestin + GRK3.

5 us phosphorylation sites for GRK1, GRK2, and GRK3.

6 We demonstrate that in addition to GRK2, GRK3-6 can phosphorylate the Y326A mutant and rescue its

7 A expression of G-protein receptor kinase-3 (GRK3), a protein involved in opioid receptor desensitiza

8 tor desensitization as a consequence of poor GRK3 activation.

9 Disruption of CREB or GRK3 activity within the NAc specifically by viral-media

10 owever, expression of GRK2 and arrestin-2 or GRK3 and arrestin-3 did not result in desensitization or

11 that KOR may activate p38 MAPK in brain by a GRK3 and arrestin-dependent mechanism.

12 requires opioid receptor phosphorylation by GRK3 and association of arrestin3 to initiate the cascad

13 ensitization, supporting the hypothesis that GRK3 and beta-arr2 effectively produce CB1 receptor dese

14 However, coexpression of GRK3 and beta-arrestin 2 (beta-arr2) caused profound hom

15 strategy, we have recently shown that GRK2, GRK3 and beta-arrestin-2 promote C3a receptor (C3aR) des

16 ansgenic mice also exhibited selectivity, as GRK3 and GRK5 desensitized in vivo alpha(1)AR mitogen-ac

17 Overall, these data suggest that GRK3 and GRK6 use different pathways to desensitize the

18 beta-arrestin2 recruitment catalyzed by both GRK3 and GRK6 whereas CCL21 activates GRK6 alone.

19 ng both G-protein-coupled receptor kinase 3 (GRK3) and beta-arrestin 2 (arr3).

20 ing site distinguishes the betaARK (GRK2 and GRK3) and GRK4 (GRK4, GRK5, and GRK6) subfamilies.

21 -arr 2), we compared the rates of beta-ARK2 (GRK3)- and beta-arr 2-mediated homologous receptor desen

22 so called G protein-coupled receptor kinase (GRK3)], and beta-arrestin 2 (beta-arr 2), we compared th

23 onally, NOPR internalization was absent when GRK3, and Arrestin3 were knocked down using siRNA, but n

24 JNK but not ERK signaling requires Ser-363, GRK3, and Arrestin3.

25 gulated in cells overexpressing either GRK2, GRK3, and GRK5 under conditions that elicited similar le

26 e receptor alone or with various GRKs (GRK2, GRK3, and GRK5).

27 rate that the T180A mutation probably blocks GRK3- and arr3-mediated desensitization of MOR by preven

28 ephalin, fentanyl, or sufentanyl, produced a GRK3- and beta-arr 2-dependent reduction in response in

29 ues 439 and 460 did not significantly affect GRK3- and beta-arr2-dependent desensitization.

30 regions of the CB1 receptor responsible for GRK3- and beta-arr2-mediated desensitization, we constru

31 esidues within this region are important for GRK3- and beta-arr2-mediated desensitization.

32 GRK2 and GRK3 are selectively regulated in vitro by free Gbetagam

33 inase 3 (GRK3) nor cell-specific deletion of GRK3/arrestin-dependent p38alpha MAPK from dopamine neur

34 neurons disrupts behavioral inhibition in a GRK3/arrestin-independent manner and suggests that KOR a

35 sion of G protein-coupled receptor kinase 3 (GRK3), beta-arrestin-1, Pyk2, and focal adhesion kinase

36 The rate of GRK3/beta-arrestin 2-dependent desensitization was reduc

37 In oocytes expressing GRK5 instead of GRK3, both [D-Ala2,N-MePhe4, Gly-ol5]enkephalin and fent

38 attenuated by concomitant overexpression of GRK3 but not GRK2 or GRK5.

39 hospholipase C (by AlF4(-)) was inhibited in GRK3- but not GRK6-overexpressing cells.

40 tion of MOR and MOR(T180A) in the absence of GRK3 coexpression.

41 r)) and a G-protein-coupled-receptor kinase (GRK3) construct (MAS-GRK3) eliminated oxo-M modulation.

42 It also induced the formation of GRK3.CXCR4 or FAK.CXCR4 complexes.

43 report that cilia preparations derived from GRK3-deficient mice lack the fast agonist-induced desens

44 to GRK2-deficient mice, which die in utero, GRK3 deletion allows for normal embryonic and postnatal

45 interact with alpha(1B)ARs in vivo such that GRK3 desensitizes all alpha(1B)AR signaling, whereas GRK

46 ), and Galpha(12/13) did not bind to GRK2 or GRK3 despite their presence in the extract.

47 orphin, KOR, or G-protein receptor kinase 3 (GRK3) did not show significant increases in KOR-P IR aft

48 xpressing the rat D1A receptor with GRK2 and GRK3 displayed a rightward shift of the dopamine dose-re

49 As is the case with mammalian GRK2 and GRK3, Drosophila GPRK1 includes a C-terminal pleckstrin

50 oupled-receptor kinase (GRK3) construct (MAS-GRK3) eliminated oxo-M modulation.

51 hese findings demonstrate the requirement of GRK3 for odorant-induced desensitization of cAMP respons

52 In contrast to GRK2, GRK3 forms a G betagamma complex after stimulation of al

53 beta1 and G beta2 but not G beta3, while the GRK3 fusion protein binds all three G beta isoforms.

54 or lacking the G-protein receptor kinase 3 (GRK3) genes.

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

56 These studies demonstrate that GRK3, GRK5, and GRK6 are also stabilized by interaction

57 proteins and multiple protein kinases [GRK2, GRK3, GRK5, GRK6 and protein kinase C (PKC)].

58 ulated by GRK2, GRK6, and arrestin3, whereas GRK3, GRK6, and arrestin2 played a primary role in posit

59 G protein-coupled receptor kinases (GRK2 and GRK3) had no effect on LL-37-induced mast cell degranula

60 brain Galpha(q/11) to bind to both GRK2 and GRK3 in an AlF(4)(-)-dependent manner.

61 agonist-stimulated translocation of GRK2 and GRK3 in an intact cellular system and demonstrates isofo

62 strate a role for GRK2 (and potentially also GRK3) in agonist-induced MOPr desensitization in the LC,

63 GRK3 is expressed to a high degree in the olfactory epit

64 protein-coupled receptor kinase 2 (GRK2) and GRK3, is the fly RK.

65 In contrast, neither prodynorphin nor GRK3 knock-out mice showed U50,488 tolerance after pSNL.

66 neurons isolated from KOR knock-out mice or GRK3 knock-out mice.

67 12-induced phosphorylation of Ser-346/7 with GRK3 knockdown having the strongest effect, while inhibi

68 In contrast to GRK3 knockout mice, GRK5 knockout mice exhibited reduced

69 In LC neurons from GRK3 knockout mice, Met-Enk-induced desensitization was

70 neurons, which have been shown to express a GRK3-like protein, abolishes desensitization of the alph

71 s demonstrates the specific involvement of a GRK3-like protein.

72 Conversely, GRK3 may cause desensitization independently of receptor

73 ptive actions after nerve injury and induced GRK3-mediated opioid tolerance.

74 the G protein-adenylyl cyclase system in the GRK3 (-/-) mice in the olfactory epithelium.

75 by fentanyl was not evident in neurons from GRK3-/- mice or neurons pretreated with small inhibitory

76 atment in neurons from wild type, MOR-/-, or GRK3-/- mice.

77 K1/2 by fentanyl and morphine was rescued in GRK3-/- neurons following transfection with dominant pos

78 bal deletion of G-protein receptor kinase 3 (GRK3) nor cell-specific deletion of GRK3/arrestin-depend

79 h these results, in vitro phosphorylation by GRK3 of KOR isolated from tolerant mice resulted in 46 +

80 Coexpression with either GRK3 or arr3 individually did not significantly enhance

81 Co-expression of either GRK3 or GRK5 along with beta-arrestin 2 significantly in

82 These results suggest that co-expression of GRK3 or GRK5 and beta-arrestin 2 produced homologous, ag

83 nificantly attenuated with either concurrent GRK3 or GRK5 overexpression.

84 receptor desensitization, mediated by either GRK3 or GRK5, at a rate dependent on agonist efficacy.

85 ciception and reward effects in mice lacking GRK3 or GRK5.

86 Overexpression of GRK3 or GRK6 enhanced M3 mACh receptor phosphorylation a

87 (mAbs) that specifically react with GRK2 and GRK3 or with GRK4, GRK5, and GRK6.

88 whereas addition of either beta-arrestin 2, GRK3, or GRK5 alone had no effect on the KOR desensitiza

89 genic mouse hearts overexpressing only GRK2, GRK3, or GRK5 had no hypertrophy.

90 K2 [commonly known as the beta-AR kinase 1], GRK3, or GRK5) with concomitant cardiac expression of a

91 ally increased in cells overexpressing GRK2, GRK3, or GRK5.

92 he heparin-sensitive kinase may not be GRK2, GRK3, or GRK6 expressed in CHO/AT1A-R cells, since angio

93 A heparin-sensitive kinase other than GRK2, GRK3, or GRK6 may be involved in the agonist-induced hom

94 f G protein-coupled receptor kinase (GRK) 2, GRK3, or GRK6 reduced CXCL12-induced phosphorylation of

95 We show that knockdown of GRK2, GRK3, or GRK6, but not GRK5, significantly increased car

96 pressing equivalent M3 mACh receptor number, GRK3- or GRK6-overexpressing cells exhibited a reduced p

97 The loss of GRK3- or PKC-mediated phosphorylation of Ser-346/7 impai

98 ed that G-protein-coupled receptor kinase 3 (GRK3; or beta-adrenergic receptor kinase 2) was not only

99 12-K(ir)3.1 and channel inhibition through a GRK3-, p38 MAPK- and Src-dependent mechanism.

100 previous study, we documented that GRK2 and GRK3 phosphorylate purified and reconstituted rat substa

101 ggest that NOPR function may be regulated by GRK3 phosphorylation of Ser-363 and Arrestin3 and furthe

102 Furthermore, GRK3 phosphorylation sites required for opioid receptor

103 Taken together, these data suggest that GRK3 plays an important role in prostate cancer progress

104 A survey of GRKs revealed that only GRK2 or GRK3 promotes D(2) DAR phosphorylation.

105 Because GRK3 requires activation and membrane targeting by free

106 Moreover, mice lacking GRK3 showed no increase in KOR-P labeling and developed

107 receptor phosphorylation and suggest a novel GRK3 site of regulation not yet described for other G-pr

108 Mechanistically, we found that GRK3 stimulated angiogenesis, at least in part through d

109 protein-coupled receptor kinase 2 (GRK2) and GRK3 "suppressed" the shutoff defect of the S --> A (391

110 meable, small-molecule inhibitor of GRK2 and GRK3, Takeda compound 101 (Cmpd101; 3-[[[4-methyl-5-(4-p

111 Furthermore, GRK3 was found to be overexpressed in human prostate can

112 hosphorylation seen in clones overexpressing GRK3 was not accompanied by increased receptor-Galpha(q/

113 xyl terminus by G-protein receptor kinase 3 (GRK3) was previously shown to be required for receptor d