ライフサイエンスコーパス: GRK5

1 of CaM for selective substrate targeting by GRK5.

2 erine 375 that was predominantly mediated by GRK5.

3 cannabinoid agonist-induced up-regulation of GRK5.

4 ocytes involving CTGF-mediated regulation of GRK5.

5 eurons are enriched in GRK2, arrestin-3, and GRK5.

6 of wild type but not catalytically inactive GRK5.

7 paBalpha in myocytes inhibited the levels of GRK5.

8 , an inhibitor of IkappaB kinase 2 decreased GRK5.

9 r polymorphisms in ADRB1, ADRB2, ADRA2C, and GRK5.

10 to identify potential nuclear substrates for GRK5.

11 tyrosine-phosphorylate and thereby activate GRK5.

12 osphorylation of membrane-bound rhodopsin by GRK5.

13 membrane binding domain in the C terminus of GRK5.

14 s and provides insight into the functions of GRK5.

15 pression of the G protein receptor kinase 5, GRK5.

16 n and reward effects in mice lacking GRK3 or GRK5.

17 on with siRNA, we demonstrated that lowering GRK5/6 abolishes IGF1-mediated ERK and AKT activation, w

18 Thus, our findings identify GRK5/6 as novel kinases for the single transmembrane rec

19 ems to be the case for the GRK2/3 subfamily, GRK5/6 effectively phosphorylate inactive forms of sever

20 G protein-coupled receptor kinases 5 and 6 (GRK5/6), traditionally known to phosphorylate and desens

21 ate that the beta2AR can signal to ERK via a GRK5/6-beta-arrestin-dependent pathway, which is indepen

22 GRK5/6-induced LRP6 activation is inhibited by the LRP6

23 suggesting that it is an inherent ability of GRK5/6.

24 at, following ventricular pressure overload, GRK5, a primary cardiac GRK, facilitates maladaptive myo

25 Mechanistically, we show that this is due to GRK5 acting, in a non-GPCR manner, as a class II histone

26 GRK5, acting in a kinase independent manner, is a facili

27 or understanding how two functional effects, GRK5 activation and localization, can cooperate under co

28 receptor kinase-5 (GRK5), but mechanisms for GRK5 activation by the PDGFRbeta remain obscure.

29 Physiologic SMC GRK5 activity also increased PDGFRbeta association with

30 GRK5 activity in the nucleus of myocytes has been shown

31 es with PAR4 inhibitors, and upregulation of GRK5 activity or signaling in platelets may have therape

32 ated phosphorylation of GRK5 correlated with GRK5 activity, as assessed by seryl phosphorylation of t

33 Molecular studies suggest that GRK5 acts in concert with NFAT to increase hypertrophic

34 the fish homologs of GRK2 and -5, Grk2/3 and Grk5, also have unique, complementary, or competitive ro

35 to a stoichiometry of 0.8 mol phosphate/mol GRK5, an extent approximately 5 times greater than obser

36 or of G-protein signaling homology domain of GRK5 and -6 and identified a peptide inhibitor with pote

37 In contrast, GRK5 and -6 mediated much less receptor phosphorylation

38 To define its function, a panel of GRK5 and -6 mutants was generated and screened by intact

39 ordering of the amphipathic alphaN-helix of GRK5 and allosteric disruption of kinase-RH domain inter

40 results suggest that p105 phosphorylation by GRK5 and binding of arrestin-2 negatively regulates LPS-

41 nanomolar IC50 values against both GRK2 and GRK5 and good selectivity against other closely related

42 phate production stimulated by H1HR, whereas GRK5 and GRK6 had lesser effects on H1HR phosphorylation

43 Unlike after TAC, swim-trained transgenic GRK5 and nontransgenic littermate control mice exhibited

44 -regulation of GRK5, but not GRK2; moreover, GRK5 and PDGFRbeta were coordinately up-regulated in SMC

45 hospholipid-dependent autophosphorylation of GRK5 and phosphorylation of membrane-bound rhodopsin by

46 NPM1 phosphorylation by GRK5 and PLK1 correlates with the sensitivity of cells t

47 aM), which leads to nuclear translocation of GRK5 and promotion of cardiac hypertrophy.

48 This domain is fully resolved in GRK5 and reveals novel interactions with the nucleotide

49 a specific site within the amino terminus of GRK5 and this interaction occurs after selective activat

50 e the mechanism underlying the regulation of GRK5 and to identify the role of GRK5 in the cannabinoid

51 PCRs and increase in the expression of RGS2, GRK5, and Arrb2.

52 assessed, including nuclear localization of GRK5, and compared with TAC.

53 G-protein signaling 2, RGS2; GPCR Kinase 5, GRK5; and beta-arrestin, Arrb2) using RT-PCR, qPCR, and

54 These results reveal that arrestin-2 and GRK5 are important negative regulatory components in TLR

55 GRK2 and GRK5 are overexpressed in the failing heart and thus hav

56 We show that GRK isoforms GRK2 and GRK5 are similarly expressed in direct and indirect path

57 In cardiomyocytes, GRK2 and GRK5 are two GRKs important for myocardial regulation, a

58 echanisms governing the nuclear targeting of GRK5 are unknown.

59 ein-coupled receptor kinases 2 (GRK2) and 5 (GRK5) are fundamental regulators of cardiac performance

60 These results define myocyte GRK5 as a critical regulator of pathological cardiac gro

61 Additionally, we have previously classified GRK5 as a determinant of left-right asymmetry and proper

62 Taken together, our results established GRK5 as a key contributor to the growth and metastasis o

63 Further, these results define GRK5 as a potential therapeutic target to limit HF devel

64 Similar to other AGC kinases, the GRK5 AST is an integral part of the nucleotide-binding p

65 ned a crystal structure of full-length human GRK5 at 1.8 A resolution.

66 n is analogous to one that can be assumed by GRK5, at least partially explaining the loss in selectiv

67 ls being less sensitive and cells with lower GRK5 being more sensitive to PLK1 inhibitor-induced apop

68 to the COOH-terminal domain of p105, whereas GRK5 binds to and phosphorylates p105.

69 In contrast, female VSM-GRK5 blood vessels have diminished betaAR-mediated dilat

70 dues by G protein-coupled receptor kinase-5 (GRK5), but mechanisms for GRK5 activation by the PDGFRbe

71 eta activation engendered down-regulation of GRK5, but not GRK2; moreover, GRK5 and PDGFRbeta were co

72 In contrast, phosphorylation of GRK5 by the PDGFRbeta enhanced the V(max) of GRK5-mediat

73 horylation is required for the activation of GRK5 by the PDGFRbeta, but not by the beta(2)-adrenergic

74 Herein, we investigated whether GRK5 can specifically regulate the NF-kappaB signaling p

75 r factor of activated T cells (NFAT) because GRK5 causes enhancement of NFAT-mediated hypertrophic ge

76 A 2.4 A crystal structure of the GRK5.CCG215022 complex was determined and revealed that

77 Here we report that GRK5 co-localizes with gamma-tubulin, centrin, and peric

78 RK5 revealed a nonsynonymous polymorphism of GRK5, common in African Americans, in which leucine is s

79 we report the architecture of the Ca(2+).CaM-GRK5 complex determined by small-angle X-ray scattering

80 ncreased expression and activity of GRK2 and GRK5 contribute to the loss of contractile reserve in th

81 In summary, we found that GRK2 and GRK5 control cardiac function as well as morphogenesis d

82 ree of PDGFRbeta-mediated phosphorylation of GRK5 correlated with GRK5 activity, as assessed by seryl

83 Altogether, these findings indicate that GRK5 deficiency accelerates beta-amyloidogenic APP proce

84 Altogether, these results suggest that GRK5 deficiency leads to a reduced hippocampal ACh relea

85 mer disease (AD), but the mechanism by which GRK5 deficiency may contribute to AD pathogenesis remain

86 We have previously demonstrated that GRK5 deficiency selectively impairs desensitization of p

87 h other supporting evidence, we propose that GRK5 deficiency selectively renders BFC neurons more vul

88 get for eliminating the pathologic impact of GRK5 deficiency.

89 G protein-coupled receptor kinase 5 (GRK5) deficiency has been linked recently to early Alzhe

90 embrane G protein-coupled receptor kinase 5 (GRK5) deficiency is linked to Alzheimer disease, yet its

91 ected the difference between the control and GRK5-deficient APPsw mice for ISF Abeta.

92 decreasing the ISF Abeta in both control and GRK5-deficient APPsw mice, failed to correct the differe

93 Global GRK5 deletion also diminished hypertrophy and related ge

94 phorylation of the same receptor by GRK2 and GRK5, demonstrating preference for the latter.

95 m of hypertrophic stimuli, thus facilitating GRK5-dependent regulation of maladaptive hypertrophy.

96 ed beta-catenin and axin2 response caused by GRK5 depletion.

97 rotein kinase C, c-Jun N-terminal kinase, or GRK5 did not inhibit the Cmpd101-insensitive component o

98 verexpression of dominant negative mutant of GRK5 (dnGRK5) in a cholinergic neuronal cell line led to

99 Finally, purified GRK5 effected agonist-dependent seryl phosphorylation of

100 female mice, VSM-specific overexpression of GRK5 elevates BP mediated by Gi and, at least in part, b

101 n embryos were rescued by this approach, but Grk5 embryos failed to respond.

102 GRK5 enhances activation of MEF2 in concert with Gq sign

103 ncreased PDGFRbeta-associated Shp2 activity, GRK5-expressing SMCs demonstrated greater PDGF-induced S

104 We show that disruption of platelet GRK5 expression by rs10886430-G is associated with enhan

105 Furthermore, increased GRK5 expression induced the phosphorylation status of p6

106 Knockdown of GRK5 expression leads to G2/M arrest, characterized by a

107 internalization was not affected by loss of GRK5 expression.

108 egulates 5-HT2A receptor signaling, enhances GRK5 expression; the phosphorylation of CB2 receptors; a

109 F-kappaB could interact with the promoter of GRK5 following myocytes NF-kappaB activation.

110 rmine the absolute requirement of endogenous GRK5 for cardiac hypertrophy and HF development after ch

111 Modulation of GRK5 function could serve as a new approach for preventi

112 To gain mechanistic insight into GRK5 function, we determined a crystal structure of full

113 Here, we demonstrate that arrestin-2 and GRK5 (G protein-coupled receptor kinase 5), proteins tha

114 NF-kappaB signaling in the regulation of the GRK5 gene and expression of this kinase in cardiomyocyte

115 models with global or cardiomyocyte-specific GRK5 gene deletion to determine the absolute requirement

116 e we report that inactivation of one copy of Grk5 gene in transgenic mice overexpressing beta-amyloid

117 onic SNPs of the G protein-coupled kinase 5 (GRK5) gene were significantly associated with postoperat

118 level of basal BRET2 using beta2AR-Rluc and GRK5-GFP2 that was not diminished by agonist stimulation

119 Arg389>Gly and G-protein receptor kinase 5 (GRK5) Gln41>Leu polymorphisms, which are more prevalent

120 imulated responses more effectively than did GRK5-Gln41 in transfected cells and transgenic mice, and

121 African Americans with ADRB1 Gly389Gly GRK5 Gln41Gln derived a similar survival benefit from be

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

123 ion by GRK2, while a comparable peptide from GRK5 had no effect on GRK2 activity.

124 For example, GRK5 has been shown to localize to centrosomes and regul

125 on of G proteinen-coupled receptor kinase-5 (GRK5) has previously been shown to possess nuclear activ

126 One member of the family, GRK5, has been implicated in several human pathologies,

127 Eight genes (TTN, BAG3, GRK5, HSPB7, MTSS1, ALPK3, NMB, and MMP11) supported by

128 In summary, we provide a snapshot of GRK5 in a partially closed state, where structural eleme

129 GRK5 in complex with the ATP analog 5'-adenylyl beta,gam

130 Corroborating a mechanism of GRK5 in CTGF-mediated control of beta-AR sensitivity, Ch

131 report that increased levels and activity of GRK5 in failing myocardium may have unique significance

132 we report an important contributory role for GRK5 in human prostate cancer.

133 Targeted cardiac elevation of GRK5 in mice leads to exaggerated hypertrophy and early

134 the present study was to examine the role of GRK5 in monomicrobial pulmonary infection by using an in

135 ulator of NF-kappaB, increased the levels of GRK5 in myocytes whereas treatment of cells with N-acety

136 In this study, we investigated the role of GRK5 in physiological, swimming-induced hypertrophy (SIH

137 Phosphorylation of the PDGFRbeta by GRK5 in smooth muscle cells or in purified protein prepa

138 tivation promoted tyrosyl phosphorylation of GRK5 in smooth muscle cells.

139 gulation of GRK5 and to identify the role of GRK5 in the cannabinoid agonist-induced up-regulation an

140 ing bacterial pneumonia but that the role of GRK5 in the clinical outcome in this model is dependent

141 significant HDAC activity can be found with GRK5 in the heart.

142 Recently, increased expression of GRK5 in the myocardium of mice has been shown to be detr

143 e human G protein-coupled receptor kinase 5 (GRK5) in yeast.

144 down of G protein-coupled receptor kinase 5 (GRK5) in zebrafish embryos resulted in the quantitation

145 In addition, overexpression of GRK2 and GRK5 increased basal levels of phosphorylation of the GR

146 ch), we found that physiologic expression of GRK5 increased PDGF-promoted PDGFRbeta seryl phosphoryla

147 We found that overexpression of GRK5 increased the levels of NF-kappaB -p50 and p65 in v

148 GRK5 inhibitors in development for the treatment of hear

149 GRK5 interaction with NPM1 is mediated by the N-terminal

150 ations, and computational docking to analyze GRK5 interaction with the beta2-adrenergic receptor (bet

151 cannabinoid agonist-induced up-regulation of GRK5 involves CB2 receptors, beta-arrestin 2, and ERK1/2

152 Although GRK5 is a critical regulator of cardiac G protein-couple

153 Our data show that GRK5 is a nuclear HDAC kinase that plays a key role in m

154 data suggest that although nuclear-localized GRK5 is a pathological mediator after stress, this nonca

155 Our data reveal that CaM binding to GRK5 is a physiologically relevant event that is absolut

156 Our studies reveal that GRK5 is able to interact with and phosphorylate nucleoph

157 artery bypass grafting, genetic variation in GRK5 is associated with postoperative AF despite periope

158 Nuclear accumulation of GRK5 is enhanced in myocytes after aortic banding in viv

159 o synaptic membranes, whereas phosphorylated GRK5 is found in plasma membrane and cytosolic fractions

160 GRK5 is highly expressed within myocardium and is upregu

161 Overall, these studies demonstrate that GRK5 is localized in the centrosome and regulates microt

162 tress, this noncanonical nuclear activity of GRK5 is not induced during physiological hypertrophy.

163 The centrosomal localization of GRK5 is observed predominantly at interphase and althoug

164 GRK5 is potently inhibited by the calcium-sensing protei

165 G protein-coupled receptor kinase 5 (GRK5) is a regulator of cardiac performance and a potent

166 G protein-coupled receptor kinase 5 (GRK5) is a serine/threonine kinase previously shown to m

167 orylation, by 3.4-fold, without altering the GRK5 K(M) for peptide.

168 Inhibition of GRK5 kinase activity attenuated the migration and invasi

169 The overall conformation of the GRK5 kinase domain is similar to that of a previously de

170 With SMCs from GRK5 knock-out and cognate wild type mice (five of each)

171 ACh release in hippocampal slices from young GRK5 knock-out mice was significantly reduced compared w

172 c degeneration and cognitive decline in aged GRK5 knock-out mice, this nonstructural alteration may b

173 or cholinergic degenerative changes in young GRK5 knock-out mice.

174 GRK5 knockdown also results in enhanced IkappaB kinase-m

175 is significantly enhanced in arrestin-2 and GRK5 knockdown cells.

176 Conversely, GRK5 knockdown inhibited Ser339 phosphorylation of CXCR4

177 lved, we tested the effect of arrestin-2 and GRK5 knockdown on LPS-stimulated signaling components th

178 With a sublethal dose of E. coli, GRK5 knockout (KO) mice exhibited higher plasma CXCL1/KC

179 In contrast to GRK3 knockout mice, GRK5 knockout mice exhibited reduced antinociceptive res

180 in inducing conditioned place preference in GRK5 knockout mice, whereas cocaine conditioned place pr

181 ne with G protein-coupled receptor kinase-5 (GRK5) knockout mice.

182 increased sensitivity of cardiomyocytes from GRK5-knockout (KO) mice to beta-adrenergic agonists, pre

183 SII in comparison to ANG, whereas those from GRK5 KO mice did not differ from those from WT mice.

184 n contrast to the reduced bacterial loads in GRK5 KO mice following a sublethal dose, at a lethal dos

185 coli, the bacterial burdens remained high in GRK5 KO mice relative to those in WT mice.

186 cardiac hypertrophy is totally prevented in Grk5 KO mice.

187 on or increased neutrophil exhaustion in the GRK5 KO mice.

188 on of inflammation advanced, in the lungs of GRK5 KO mice.

189 knockout mice (KO) and to a lesser extent in Grk5 KO mice.

190 to beta-adrenergic agonists, pretreatment of GRK5-KO cardiomyocytes with rec-hCTGF, as opposed to car

191 interval [CI]: 1.1 to 3.7, p = 0.03) whereas GRK5 Leu41 was associated with improved survival in Afri

192 showed a pharmacogenomic interaction between GRK5-Leu41 and beta-blocker treatment, in which the pres

193 cker treatment, in which the presence of the GRK5-Leu41 polymorphism was associated with decreased mo

194 frican-American subjects with heart failure, GRK5-Leu41 protected against death or cardiac transplant

195 , and, like pharmacological betaAR blockade, GRK5-Leu41 protected against experimental catecholamine-

196 tion of excessive catecholamine signaling by GRK5-Leu41 provides a 'genetic beta-blockade' that impro

197 GRK5-Leu41 uncoupled isoproterenol-stimulated responses

198 o undergo apoptosis with cells having higher GRK5 levels being less sensitive and cells with lower GR

199 d that transgenic mice with elevated cardiac GRK5 levels have exaggerated hypertrophy and early heart

200 stimulation of GRK site phosphorylation and GRK5 levels while being depleted of GRK2 and GRK6.

201 vent that is absolutely required for nuclear GRK5 localization downstream of hypertrophic stimuli, th

202 hile the endothelin-1 does not cause nuclear GRK5 localization.

203 identified a single sentinel variant in the GRK5 locus (rs10886430-G, p = 3.0 x 10(-42)) associated

204 Depletion of GRK5 markedly reduces Wnt3A-stimulated LRP6 phosphorylat

205 ing mechanisms underlying an increase in VSM-GRK5 may have a profound influence on the use and develo

206 Common variants in GRK5 may modify clinical outcomes with PAR4 inhibitors,

207 GRK5-mediated desensitization of PDGFRbeta inositol phos

208 In this study, we have found that GRK5-mediated pathological cardiac hypertrophy involves

209 GRK5 by the PDGFRbeta enhanced the V(max) of GRK5-mediated peptide phosphorylation, by 3.4-fold, with

210 hosphorylation of GRK5 was not necessary for GRK5-mediated phosphorylation of the beta(2)-adrenergic

211 On the basis of the level of GRK5-mediated phosphorylation we observe in isolated mem

212 We conclude that GRK5 mediates the preponderance of PDGF-promoted seryl p

213 hough only the C domain interaction disrupts GRK5 membrane association, thereby facilitating cytoplas

214 Further, SIH in post-TAC transgenic GRK5 mice was able to preserve cardiac function.

215 VSM-GRK5 mice were hypertensive, with a 25% to 35% increase

216 This Grk5 morphant phenotype was associated with an overall d

217 inus of GRK5 negating CaM binding attenuates GRK5 movement from the sarcolemma to the nucleus and, im

218 oci (C1orf198, PLEK, OSMR-AS1, NUGGC/SCARA5, GRK5, MPHOSPH9, ARID4A, PLCG2, SMG6, EIF5A, and STX10) o

219 decreased the stimulated increased levels of GRK5 mRNA and protein.

220 cells expressing a tyrosine-to-phenylalanine GRK5 mutant, and in GRK5 peptide phosphorylation assays.

221 independently to two helical regions at the GRK5 N and C termini to inhibit GPCR phosphorylation, th

222 ly to the small lobe of the kinase domain of GRK5 near elements critical for receptor interaction and

223 A mutation within the amino-terminus of GRK5 negating CaM binding attenuates GRK5 movement from

224 Overall, our data suggest that GRK5 negatively regulates CXCL1/KC levels during bacteri

225 The GRK5 NLT is largely displaced from its previously observ

226 Moreover, these MR-dependent GRK2 and GRK5 non-canonical activities appear to involve cross-ta

227 We report here that GRK5 nuclear accumulation is dependent on Ca(2+)/calmodu

228 Mechanistically, SIH did not lead to GRK5 nuclear accumulation, which was confirmed in vitro

229 nsverse aortic constriction (TAC) because of GRK5 nuclear accumulation.

230 In cells, malbrancheamide attenuated GRK5 nuclear translocation and effectively blocked the h

231 siological hypertrophy, was unable to induce GRK5 nuclear translocation in myocytes.

232 Complimentary to this, GRK5 null mice exhibit less NFAT transcriptional activit

233 ted greater PDGF-induced Src activation than GRK5-null cells.

234 The influence of GRK5 on NF-kappaB expression and activity was dependent

235 Interestingly, overexpression of GRK5 or -6 increased mutant receptor phosphorylation and

236 of NFATc3 expression in the heart protected GRK5 overexpressing transgenic mice from the exaggerated

237 Transgenic mice with cardiomyocyte-specific GRK5 overexpression activate an NFAT-reporter in mice ba

238 red gene expression between TAC and SIH with GRK5 overexpression.

239 yrosine-to-phenylalanine GRK5 mutant, and in GRK5 peptide phosphorylation assays.

240 Taken together, our results demonstrate that GRK5 phosphorylates Ser-4 in nucleophosmin and regulates

241 fied amino acid T66 of moesin as a principal GRK5 phosphorylation site and showed that enforcing the

242 In contrast to GRK5, physiologic GRK2 activity did not alter PDGFRbeta/

243 The two most widely expressed GRKs (GRK2 and GRK5) play a role in cardiovascular disease and thus rep

244 on of the beta2AR and GRK5, we conclude that GRK5 plays a distinctive role in the phosphorylation of

245 G protein-coupled receptor kinase 5 GRK5 plays a key role in regulating cardiac signaling an

246 G protein-coupled receptor kinase 5 (GRK5) plays a key role in cardiac signaling regulation,

247 icles, and the hearts of embryos depleted in Grk5 present with a generalized atrophy.

248 Importantly, siRNA against GRK5 presented with the opposite results in neonatal rat

249 y the N-terminal domain of each protein, and GRK5 primarily phosphorylates NPM1 at Ser-4, a site shar

250 eptor kinase 2 (GRK2) pro-death activity and GRK5 pro-hypertrophic action.

251 Restoration of wild-type GRK5 promoted Ser339 phosphorylation of CXCR4 and inhibi

252 te that G protein-coupled receptor kinase 5 (GRK5) promotes platelet activation specifically via PAR4

253 ed CP55940 exposure selectively up-regulates GRK5 proteins in rat PFCx and in a neuronal cell culture

254 GRK5 regulated the subcellular distribution of moesin an

255 ignals, demonstrating that nuclear localized GRK5 regulates gene transcription via a pathway critical

256 Expression of GRK5 rescues the diminished beta-catenin and axin2 respo

257 complex with GRK5, revealing how CaM shapes GRK5 response to calcium.

258 nd p65 in vitro and in vivo, whereas loss of GRK5 resulted in lower cardiac NF-kappaB levels.

259 In zebrafish, functional knock-down of GRK5 results in reduced Wnt signaling, analogous to LRP6

260 Re-sequencing of GRK2 and GRK5 revealed a nonsynonymous polymorphism of GRK5, comm

261 d biochemical analysis of a CaM complex with GRK5, revealing how CaM shapes GRK5 response to calcium.

262 e supporting the possible involvement of the GRK5/RGS10 locus in ARM.

263 3 and the C terminus of the beta2AR with the GRK5 RH bundle subdomain, membrane-binding surface, and

264 involves large conformational changes in the GRK5 RH/catalytic domain interface upon receptor binding

265 By introducing point mutations in the GRK5 RHD-kinase domain interface, we show with both in s

266 rophic gene transcription in the nucleus via GRK5's ability to bind DNA directly without a phosphoryl

267 In the nucleus, GRK5's newly discovered kinase activity on histone deace

268 Most importantly, we found that GRK5 shRNA lentiviral particle treatment prevented the c

269 enomena were also significantly inhibited by GRK5 shRNA lentiviral treatment.

270 at knockdown of GRK2, GRK3, or GRK6, but not GRK5, significantly increased carbachol-mediated calcium

271 a xenograft model of human prostate cancer, GRK5 silencing reduced tumor growth, invasion, and metas

272 nd small interfering RNA (siRNA) knockdown], GRK5 (siRNA knockdown), and beta-arrestin1 (siRNA knockd

273 The GRK5 subcellular distribution in the human striatal neur

274 rane attachment protein moesin as a putative GRK5 substrate.

275 teraction for phosphorylation of cytoplasmic GRK5 substrates.

276 th conditional, cardiac-specific deletion of GRK5 that also demonstrated similar protection from path

277 r localization as overexpression of a mutant GRK5 that cannot enter the nucleus was devoid of NF-kapp

278 e or in mice with overexpression of a mutant GRK5 that is excluded from the nucleus.

279 -adrenergic receptor, and that by activating GRK5, the PDGFRbeta triggers its own desensitization.

280 Both GRK2 and GRK5, the predominant GRKs expressed in the heart, have

281 First, in analyzing the 5'-flanking DNA of GRK5, the presence of a potential NF-kappaB binding site

282 s with phenylephrine or angiotensinII causes GRK5 to leave the sarcolemmal membrane and accumulate in

283 ooth muscle (VSM)-specific overexpression of GRK5 to recapitulate a selective aspect of hypertension

284 B plays a critical role in the regulation of GRK5 transcription in myocytes and that this may transla

285 Cardiac-specific GRK5 transgenic mice and nontransgenic littermate contro

286 We conclude that GRK5 tyrosyl phosphorylation is required for the activat

287 osphorylation, it has been demonstrated that GRK5, unlike GRK2, can reside in the nucleus of myocytes

288 tes that a novel pathological consequence of GRK5 up-regulation in the injured and failing heart is t

289 We thus aimed to identify GRK5 variants of functional significance by analysing 18

290 The CaM N domain strongly activates GRK5 via ordering of the amphipathic alphaN-helix of GRK

291 However, tyrosyl phosphorylation of GRK5 was not necessary for GRK5-mediated phosphorylation

292 Purified GRK5 was tyrosine-phosphorylated by the wild-type PDGFRb

293 tions and co-localization of the beta2AR and GRK5, we conclude that GRK5 plays a distinctive role in

294 Mice with global deletion of GRK5 were subjected to transverse aortic constriction.

295 vels of G protein-coupled receptor kinase 5 (GRK5) were found isoform-selective upregulated in both c

296 demonstrate crosstalk among WIP1, CXCR4 and GRK5, which may be important for the aggressive phenotyp

297 ound to inhibit rhodopsin phosphorylation by GRK5 with an IC(50) of approximately 30 microM.

298 entified two moderately frequent variants in GRK5 with minor allele frequencies <10%, and seven very

299 Association of GRK5 with the beta2AR in intact cells was demonstrated b

300 data has uncovered noncanonical activity of GRK5 within nuclei that plays a key role in pathological