ライフサイエンスコーパス: GRK

1 GRK phosphorylation of the beta2AR in the washed membran

2 GRKs have also been implicated in phosphorylating other

3 ment of G protein-coupled receptor kinase-2 (GRK(2)) or beta-arrestin to PAR(2), consistent with its

4 ession, G-protein-coupled receptor kinase-2 (GRK-2) membranous translocation, and D1 receptor serine

5 We have found that arrestin 2 and 3, GRK 2 and 3, 14-3-3 epsilon, and spinophilin directly as

6 hree distinct nucleotide-binding states of a GRK but also two key structural elements believed to be

7 y of GRK2 inhibitors to impart efficacy on a GRK-dependent process in cells.

8 Here we describe that a GRK contributes to Smoothened-mediated signaling in vert

9 Together, these data suggest that a GRK functions as a vertebrate kinase for Smoothened, pro

10 ng that G protein-coupled receptors activate GRKs by inducing kinase domain closure.

11 study is likely common to all GPCR-activated GRKs.

12 GRK2 confirms that the catalytic core of all GRKs consists of intimately associated kinase and regula

13 Although GRK binding to activated GPCRs results in kinase activat

14 not major determinants of selectivity among GRK subfamilies.

15 GRK1 kinase domain that are conserved among GRKs but not in the extended protein kinase A, G, and C

16 nificantly alter potency of inhibition among GRKs, it exhibited 20-fold lower inhibition of serotonin

17 isms underlying paroxetine selectivity among GRKs.

18 n between PKA phosphorylation of beta2AR and GRK-promoted events was identified by beta-arrestin-2 re

19 r studies revealed distinct roles of PKA and GRK phosphorylation of the beta(2)AR for agonist dose-de

20 - 0.009/min; t(1/2) = 1.6 min), than PKA and GRK site dephosphorylation, respectively, clearly dissoc

21 ermine the relative contribution of PKA- and GRK-mediated phosphorylation of beta(2)AR to the recepto

22 define the relative contribution of PKC and GRK to CXCR4 signaling attenuation by studying their eff

23 receptor kinases (GRKs) targeting S471, and GRK inhibitors delayed epithelial packing and junction m

24 , we found no differences between the WT and GRK(-) receptors.

25 We found that both wild-type (WT) and GRK(-) receptors underwent a similar degree of agonist-i

26 l-free assay with membrane-bound beta2AR and GRKs.

27 e of downstream effector (Gs, beta-arrestin, GRK) interactions or stabilization of specific receptor

28 it appears that association with arrestins, GRKs, 14-3-3 epsilon, and spinophilin may be important m

29 se and that the associations with arrestins, GRKs, or 14-3-3 epsilon are blocked in the presence of s

30 ity, and altered signal transduction such as GRK (g-protein receptor kinase) signaling, renin angiote

31 ed principal component analysis of available GRK and protein kinase A crystal structures to identify

32 Because GRK isoforms vary in their regulation, this partially re

33 the full range of responses, the beta2PKA(-)/GRK(-) airways had the greatest relaxation efficiency, i

34 Both GRK isoforms are abundant in the nucleus of human striat

35 of serine 348 led to an elimination of both GRK and beta-arrestin recruitment to APJ induced by apel

36 Although both GRKs also contain putative phosphorylation sites for PKC

37 hat enhanced phosphorylation of beta(2)AR by GRK and resultant increase in G(i)-biased beta(2)AR sign

38 imple model systems, CB1R is desensitized by GRK phosphorylation at two serine residues (S426 and S43

39 w that enhanced beta(2)AR phosphorylation by GRK, in addition to PKA, leads the receptor to G(i)-bias

40 eceptor signaling may be finely regulated by GRK in physiological settings.

41 ring of paroxetine is better accommodated by GRKs.

42 ng and degradation, mirroring alterations by GRKs.

43 r phosphorylation that is solely mediated by GRKs.

44 r pressure overload, GRK5, a primary cardiac GRK, facilitates maladaptive myocyte growth via novel nu

45 raction with Galpha(q/11), did not affect Ce-GRK-2 chemosensory function, disruption of the predicted

46 GPCR-bound conformation, also eliminated Ce-GRK-2 chemosensory function.

47 ctivated GPCRs, eliminated the ability of Ce-GRK-2 to restore chemosensory signaling.

48 rupting interaction between the predicted Ce-GRK-2 amino-terminal alpha-helix and kinase domain, posi

49 holipids revealed that both contribute to Ce-GRK-2 function in vivo.

50 interactions required for proper in vivo Ce-GRK-2 function.

51 at the SD3 mutant did not drive constitutive GRK desensitization.

52 creened by intact-cell assay of constitutive GRK phosphorylation of the beta(2)-adrenergic receptor (

53 ht residues results in a receptor construct, GRK(-), that is completely devoid of agonist-promoted GR

54 Therefore, agonist-dependent (GRK- and PKC-mediated) and agonist-independent (PKC-prom

55 the in vivo contribution of these described GRK structural domains and interactions to proper GRK fu

56 ereby endogenous agonists activate different GRK isoforms leads to functionally distinct pools of bet

57 58747 and 10 other inhibitors with different GRK subfamily selectivities and with either the paroxeti

58 nse to receptor phosphorylation by different GRKs has distinct functional potentials.

59 This differential GRK activation leads to distinct functional consequences

60 by agonist-selective recruitment of distinct GRK isoforms that influence different opioid-related beh

61 cate that CXCR1 and CXCR2 couple to distinct GRK isoforms to mediate and regulate inflammatory respon

62 evidence that, in contrast to current dogma, GRKs can (at least in some instances) constitutively pho

63 framework that helps evaluate how close each GRK structure is to being a catalytically competent stat

64 nger-generating enzymes and other effectors, GRKs phosphorylate activated receptors, and arrestins su

65 We monitor endogenous GRK activity with a fluorescence resonance energy transf

66 bout the cellular localization of endogenous GRKs.

67 promote this interaction, thereby enhancing GRK activity.

68 ontrolled by GPCR-kinases (GRK), we explored GRKs as potential anticancer therapeutic targets to disc

69 lls use different subsets of their expressed GRKs to promote beta-arrestin recruitment, with signific

70 The two most widely expressed GRKs (GRK2 and GRK5) play a role in cardiovascular disea

71 egulatory roles of the four widely expressed GRKs on IGF-1R signaling/degradation.

72 translocation, PKC activity and expression, GRK-2 sequestration, and D1 receptor serine phosphorylat

73 We describe here a cell-free assay for GRK phosphorylation of the beta2AR in a postnuclear 600g

74 aroxetine scaffold as the most effective for GRK inhibition in living cells, confirming that GRK2 pre

75 -adrenergic receptor were also important for GRK-dependent phosphorylation.

76 sidues in helix 8 of GPCRs are important for GRK-dependent phosphorylation.

77 These results reveal a novel role for GRK-mediated phosphorylation in regulating the post-endo

78 This study demonstrates distinct roles for GRK isoforms in IGF-1R signaling through beta-arrestin b

79 ical receptor, as a model to test functional GRK specificity.

80 desensitize betaARs, suggesting that genetic GRK variants might modify outcomes in these syndromes.

81 years, the molecular architecture of a GPCR/GRK complex remains poorly defined.

82 in-coupled receptors (GPCRs) by GPCRkinases (GRKs) promotes their desensitization and internalization

83 ribution of the TGFalpha-like ligand Gurken (GRK), a crucial ligand for axis formation, underlies EGF

84 The selectivity of balanol among human GRKs is assessed.

85 tion, hypertension, and cardiac hypertrophy, GRKs have been intensively studied as potential diagnost

86 As changes in GRK expression have featured prominently in many cardiov

87 ellular compartment-dependent differences in GRK/arrestin-mediated desensitization and signaling.

88 aused a rapid maximal 10-15-fold increase in GRK site phosphorylation of the beta2AR (t1/2 = 1 min) w

89 inuous surface that is uniquely available in GRKs for protein-protein interactions.

90 kinase activation are intimately coupled in GRKs.

91 mutation of serine 348 resulted in inactive GRK/beta-arrestin.

92 consequences of this G protein-independent, GRK/beta-arrestin-dependent signaling are largely unknow

93 complex with GRK1, the most weakly inhibited GRK tested.

94 In contrast, inhibiting GRK 5 or 6 expression abolishes beta-arrestin-mediated E

95 sphorylation, (ii) the SD3 mutation inhibits GRK-mediated desensitization although it supports some a

96 Interestingly, GRK-2 was also found to interact with and promote the ph

97 g fraction and washed membranes by intrinsic GRK activity using the GRK phosphosite-specific antibody

98 The beta-AR receptor kinase GRK-2 was also increased in HF (173 +/- 38% of control,

99 ed with the expression level of GPCR kinase (GRK) 2, the predominant GRK isoform upregulated in the f

100 the protein kinase C (PKC) and GPCR kinase (GRK) families, although the relative contribution of eac

101 ling is primarily regulated via GPCR kinase (GRK)-mediated phosphorylation of activated receptors.

102 Raf1 and G protein-coupled receptor kinase (GRK) 2 are direct interaction partners of RKIP and thus

103 ckdown of G protein-coupled receptor kinase (GRK) 2, GRK3, or GRK6 reduced CXCL12-induced phosphoryla

104 in 1/2 or G protein-coupled receptor kinase (GRK) 2/5/6, as determined by bioluminescence resonance e

105 tion by a G-protein-coupled receptor kinase (GRK) and interaction of the phosphorylated receptor with

106 2 and the G protein-coupled receptor kinase (GRK) site phosphoserines 355 and 356 of the beta2-adrene

107 GRK2 is a G protein-coupled receptor kinase (GRK) that is broadly expressed and is known to regulate

108 of human G protein-coupled receptor kinase (GRK)-6, a key regulator of dopaminergic signaling and ly

109 nd 364 in G protein-coupled receptor kinase (GRK)-mediated phosphorylation and desensitization of bet

110 e role of G protein-coupled receptor kinase (GRK)-mediated phosphorylation in agonist-induced desensi

111 nt on the G protein-coupled receptor kinase (GRK)-mediated phosphorylation of the receptors, which on

112 ulation), G protein-coupled receptor kinase (GRK)-mediated receptor phosphorylation, beta-arrestin re

113 s bind to G protein-coupled receptor kinase (GRK)-phosphorylated seven transmembrane receptors, desen

114 and V(1A)/G protein-coupled receptor kinase (GRK)/beta-arrestin signaling cascades were inhibited to

115 on of the G protein-coupled receptor kinase (GRK)/ss-arrestin system.

116 yocardial G protein-coupled receptor kinase (GRK)2 is a critical regulator of cardiac beta-adrenergic

117 cytosolic G protein-coupled receptor kinase (GRK)2 to agonist-stimulated beta-adrenergic receptors (b

118 ly to the G protein-coupled receptor kinase (GRK)2, whereas CXCR2 interacts with GRK6 to regulate cel

119 gen regulation of G protein receptor kinase (GRK); pretreatment of ovary-intact female mice with the

120 interaction and controlled by GPCR-kinases (GRK), we explored GRKs as potential anticancer therapeut

121 G protein-coupled receptor kinases (GRK) regulate diverse cellular functions ranging from me

122 cking, emphasizing the role of GPCR kinases (GRKs) and arrestins in this process.

123 C terminus of the receptor by GPCR kinases (GRKs) and by coupling of beta-arrestin 1 (betaarr1, also

124 GPCR kinases (GRKs) are responsible for GPCR phosphorylation and, ther

125 The GPCR kinases (GRKs) curtail G-protein signaling and target receptors f

126 n-coupled receptors (GPCRs) by GPCR kinases (GRKs) facilitates arrestin binding and receptor desensit

127 n-coupled receptors (GPCRs) by GPCR kinases (GRKs) functions to turn off G-protein signaling and turn

128 n-coupled receptors (GPCRs) by GPCR kinases (GRKs) is a major mechanism of desensitization of these r

129 Arrestins, GPCR kinases (GRKs), 14-3-3 proteins, and spinophilin interact with GP

130 ith heterotrimeric G proteins, GPCR kinases (GRKs), and arrestins.

131 ling pathways are regulated by GPCR kinases (GRKs), and GRK2 has been shown to be a critical molecule

132 of receptors is controlled by GPCR kinases (GRKs), some of which have been implicated in heart failu

133 Rs is their phosphorylation by GPCR kinases (GRKs).

134 ty is regulated by a family of GPCR kinases (GRKs).

135 G protein-coupled receptor (GPCR) kinases (GRKs) are critical regulators of cellular signaling and

136 G protein-coupled receptor (GPCR) kinases (GRKs) are responsible for initiating desensitization of

137 G-protein-coupled receptor (GPCR) kinases (GRKs) are serine/threonine kinases that desensitize agon

138 G-protein-coupled receptor (GPCR) kinases (GRKs) bind to and phosphorylate GPCRs, initiating the pr

139 h G protein-coupled receptor (GPCR) kinases (GRKs) have been shown to mediate desensitization of nume

140 G protein-coupled receptor (GPCR) kinases (GRKs) instigate the desensitization of activated GPCRs v

141 G protein-coupled receptor (GPCR) kinases (GRKs) phosphorylate activated GPCRs and initiate their d

142 G protein-coupled receptor (GPCR) kinases (GRKs) phosphorylate activated heptahelical receptors, le

143 G protein-coupled receptor (GPCR) kinases (GRKs) play a key role in homologous desensitization of G

144 G protein-coupled receptor (GPCR) kinases (GRKs) play a key role in terminating signals initiated b

145 G protein-coupled receptor (GPCR) kinases (GRKs) selectively recognize and are allosterically regul

146 G protein-coupled receptor (GPCR) kinases (GRKs) specifically phosphorylate agonist-occupied GPCRs

147 G protein-coupled receptor (GPCR) kinases (GRKs) were discovered by virtue of their ability to phos

148 o G protein-coupled receptor (GPCR) kinases (GRKs), particularly GRK2.

149 f G protein-coupled receptor (GPCR) kinases (GRKs), which regulate GPCR signaling, are associated wit

150 ecause GPCR phosphorylation by GPCR-kinases (GRKs) governs interactions of the receptors with beta-ar

151 G protein-Coupled Receptors (GPCRs) kinases (GRKs) play a crucial role in regulating cardiac hypertro

152 s of the G protein-coupled receptor kinases (GRKs) 2, 3, 5, and 6, as well as beta-arrestin 1.

153 G protein-coupled receptor kinases (GRKs) and arrestins mediate desensitization of G protein

154 The G protein-coupled receptor kinases (GRKs) and beta-arrestins, families of molecules essentia

155 ates are G protein-coupled receptor kinases (GRKs) and Regulators of G protein signaling (RGSs), deac

156 ins, the G-protein-coupled receptor kinases (GRKs) and the arrestins.

157 PCRs) by G protein coupled receptor kinases (GRKs) and the subsequent recruitment of beta-arrestins a

158 G protein-coupled receptor kinases (GRKs) are attractive targets for developing therapeutics

159 G protein-coupled receptor kinases (GRKs) are dynamic regulators of cellular signaling.

160 G protein-coupled receptor kinases (GRKs) are important regulators of G protein-coupled rece

161 G protein-coupled receptor kinases (GRKs) are key regulators of signal transduction that spe

162 G protein-coupled receptor kinases (GRKs) are members of the protein kinase A, G, and C fami

163 G protein-coupled receptor kinases (GRKs) are negative regulators of signaling that specific

164 PKA) and G protein-coupled receptor kinases (GRKs) desensitize beta2-adrenergic receptor (beta2AR) si

165 G protein-coupled receptor kinases (GRKs) desensitize betaARs, suggesting that genetic GRK v

166 role of G protein-coupled receptor kinases (GRKs) in agonist-induced desensitization of the mu-opioi

167 ifferent G protein-coupled receptor kinases (GRKs) in CXCR1- and CXCR2-mediated cellular functions.

168 ement of G protein-coupled receptor kinases (GRKs) in opioid dependence in addition to their roles in

169 G protein-coupled receptor kinases (GRKs) phosphorylate activated G protein-coupled receptor

170 G protein-coupled receptor kinases (GRKs) phosphorylate activated receptors to promote arres

171 G protein-coupled receptor kinases (GRKs) phosphorylate agonist-occupied receptors initiatin

172 G protein-coupled receptor kinases (GRKs) phosphorylate the activated form of G protein-coup

173 G protein-coupled receptor kinases (GRKs) play a central role in regulating receptor signali

174 G protein-coupled receptor kinases (GRKs) play a pivotal role in receptor regulation.

175 G protein-coupled receptor kinases (GRKs) regulate cell signaling by initiating the desensit

176 amily of G-protein-coupled receptor kinases (GRKs) regulate cell signaling by phosphorylating heptahe

177 G protein-coupled receptor kinases (GRKs) specifically phosphorylate activated G protein-cou

178 entified G-protein-coupled receptor kinases (GRKs) targeting S471, and GRK inhibitors delayed epithel

179 lso dock G protein-coupled receptor kinases (GRKs) that help mediate receptor desensitization.

180 OPRs) by G protein-coupled receptor kinases (GRKs), followed by arrestin binding, is thought to be a

181 ptors by G protein-coupled receptor kinases (GRKs), followed by binding of arrestin proteins, which p

182 G protein-coupled receptor kinases (GRKs), in concert with beta-arrestins, classically desen

183 iated by G protein-coupled receptor kinases (GRKs), some of which are upregulated in the failing hear

184 ation by G-protein-coupled receptor kinases (GRKs).

185 Unlike most other AGC kinases, GRKs rely on their interaction with GPCRs for activation

186 een shown, that arrestins and GPCR kinases, (GRKs) not only desensitize G protein-dependent receptor

187 a(2)AR (WT-TG) or a mutant beta(2)AR lacking GRK sites (GRK-TG) led to exaggerated cardiac response t

188 ar signaling, Caenorhabditis elegans lacking GRK-2 function are not hypersensitive to chemosensory st

189 We identified the major, likely GRK-dependent, phosphorylation cluster responsible for a

190 in-mediated ERK activation, whereas lowering GRK 2 or 3 leads to an increase in this signaling.

191 receptor kinase 2 (GRK2) is 1 of 7 mammalian GRKs that phosphorylate ligand-bound 7-transmembrane rec

192 Although many GRK structures have been reported, the mechanisms underl

193 It is widely assumed that most GRKs selectively phosphorylate only active GPCRs.

194 mice also validate the approach of mutating GRK phosphorylation sites involved in desensitization as

195 whereas the MAPK p38 acted as a noncanonical GRK that phosphorylated the formyl peptide receptor FPR1

196 Furthermore, neither PKA nor GRK site mutated receptors displayed sensitivity to the

197 itor with potential for specific blockade of GRK-mediated phosphorylation of receptors.

198 iscovery of potent and selective families of GRK inhibitors based on either the paroxetine or GSK1807

199 erived sediment accelerated the infilling of GRK after 6 ka when the Indus delta started to grow.

200 determined, the mechanism of interaction of GRK with GPCRs is currently unknown.

201 Our data demonstrate that (i) the lack of GRK sites does not impair PKA site phosphorylation, (ii)

202 ts that revealed nearly equivalent levels of GRK site phosphorylation in the plasma membrane and vesi

203 Although loss of GRK function usually results in enhanced cellular signal

204 Thus, loss of GRK-2 function may lead to changes in gene expression, v

205 ively little is known about the mechanism of GRK/GPCR interaction or how this interaction results in

206 Although the general mechanisms of GRK-arrestin regulation have been well explored in model

207 Consistent with the slow rate of GRK site dephosphorylation, the phosphatase inhibitors c

208 t and transgenic mice to explore the role of GRK-arrestin regulation of GPCRs in vivo.

209 oteins, much less is known about the role of GRK-arrestin regulation of receptors in physiological an

210 s retained the 10-15-fold ISO stimulation of GRK site phosphorylation and GRK5 levels while being dep

211 Stimulation of GRK site phosphorylation by a range of partial agonists

212 n caused an increase in the translocation of GRK-2 from cytosol to the plasma membrane.

213 g as a primary event linking upregulation of GRK to cardiac maladaptive remodeling, failure and cardi

214 GPCR activation of GRKs involves an allosteric site on GRKs distinct from t

215 ptors phosphorylated by different classes of GRKs.

216 gonist activation but also the complement of GRKs in the cell regulate formation of the arrestin-rece

217 r expression and subcellular distribution of GRKs and arrestins in the brain is largely unknown.

218 on efficiency, indicating a graded effect of GRKs as agonist concentration increased.

219 Inhibition of GRKs by using heparin or GRK2-mutant mice did not block

220 Interaction of GRKs with activated receptors serves to stimulate their

221 eart failure, leads to the overexpression of GRKs and maladaptive downregulation of GPCRs on the cell

222 The extreme N-terminal region of GRKs is clearly involved in this process, but its role i

223 ew our evolving understanding of the role of GRKs in cardiovascular pathophysiology.

224 To further elucidate the role of GRKs in regulating GPCR-mediated behaviors, we utilized

225 Although the canonical role of GRKs is to desensitize G protein-coupled receptors via p

226 ns and potential pathophysiological roles of GRKs and arrestins in human disorders as well as on rece

227 data demonstrate the relative selectivity of GRKs for the beta2AR in ASM and the ability to exploit G

228 However, the specificity of GRKs for recruiting beta-arrestins to specific receptors

229 GRK6 is a member of the GRK4 subfamily of GRKs, which is represented in most, if not all, metazoan

230 A survey of GRKs revealed that only GRK2 or GRK3 promotes D(2) DAR p

231 ation of GRKs involves an allosteric site on GRKs distinct from the catalytic site.

232 n WT and mutated beta2ARs lacking PKA and/or GRK phosphorylation sites on ASM at approximately 4-fold

233 he interaction between APJ with G protein or GRK/beta-arrestin and their downstream signaling.

234 of 130 nM, >700-fold selectivity over other GRK subfamilies, and no detectable inhibition of ROCK1.

235 potency and selectivity for GRK2 over other GRK subfamilies, PKA, and ROCK1.

236 and N-lobe not previously observed in other GRKs.

237 om its previously observed position in other GRKs.

238 ding pocket, a feature not observed in other GRKs.

239 greater than 230-fold selectivity over other GRKs and kinases.

240 e structure of GRK4alpha is similar to other GRKs, although slight differences exist within the RGS h

241 to 50-fold selectivity for GRK2 versus other GRKs.

242 and failing heart, inhibition of overactive GRKs has been proposed as a novel therapeutic approach t

243 evel of GPCR kinase (GRK) 2, the predominant GRK isoform upregulated in the failing heart.

244 Both GRK2 and GRK5, the predominant GRKs expressed in the heart, have been shown to be upreg

245 hat is completely devoid of agonist-promoted GRK-mediated receptor phosphorylation.

246 tructural domains and interactions to proper GRK function in signal regulation.

247 In addition to G protein-coupled receptors, GRKs displayed a more diverse protein/protein interactio

248 hile the X-ray crystal structures of several GRKs have been determined, the mechanism of interaction

249 beta-arrestin recruitment, with significant GRK redundancy evident in both cell types.

250 Since GRK and arrestins demonstrate no strict receptor specifi

251 TG) or a mutant beta(2)AR lacking GRK sites (GRK-TG) led to exaggerated cardiac response to pressure

252 Slow GRK site dephosphorylation after antagonist treatment wa

253 elix and kinase domain, posited to stabilize GRKs in their active ATP- and GPCR-bound conformation, a

254 By suppressing GRK expression with siRNA, we demonstrated that lowering

255 The sustained GRK/arrestin-dependent desensitization is another way in

256 bovine retina phosphorylated the FLAG-tagged GRKs in the presence of dibutyryl-cAMP, suggesting that

257 activation is dependent upon C-terminal tail GRK phosphorylation sites of the beta1AR and recruitment

258 Furthermore, we demonstrate that GRK from D. willistoni rescues a grk-null D. melanogaste

259 These results demonstrate that GRK-2 modulates 5-HT metabolism by regulating AMX-2 func

260 Here, we establish that GRK/beta-arrestin-mediated signal transduction via the a

261 ntinuous agonist stimulation indicating that GRK site dephosphorylation was minimal.

262 We show that GRK isoforms GRK2 and GRK5 are similarly expressed in di

263 We also find that GRKs phosphorylate the Na(+),K(+)-ATPase in vitro on its

264 bsequent to agonist-induced endocytosis, the GRK(-) construct exhibited less recycling in comparison

265 355, 356, and 364 play a pivotal role in the GRK-mediated desensitization, beta-arrestin binding, and

266 Moreover, multiple members of the GRK family are able to phosphorylate the beta(2)AR and i

267 GRK2 is unique among members of the GRK family in that its genetic ablation causes embryonic

268 sis of both the RH and kinase domains of the GRK family, we identified an important cluster encompass

269 Disruption of the GRK phosphorylation sites on the beta(2)AR blocked recep

270 ver, both inhibited dephosphorylation of the GRK sites after the addition of antagonist.

271 In addition, dephosphorylation of the GRK sites by intrinsic phosphatase activity occurred onl

272 Dephosphorylation of the GRK sites in intact cells after treatment with 1.0 micro

273 its mechanism of inhibition for each of the GRK subfamilies and then determined the atomic structure

274 ars to be due to a greater propensity of the GRK(-) receptors to down-regulate once internalized.

275 the receptor or membrane association of the GRK, suggesting that it is an inherent ability of GRK5/6

276 udies of the subcellular localization of the GRK-phosphorylated beta2AR on sucrose gradients that rev

277 s throughout the post-glacial history of the GRK.

278 ze a previously unidentified function of the GRK/arrestin system in mediating opioid regulation in re

279 We attempted to rescue the GRK loss-of-function heart phenotypes by downstream acti

280 Surprisingly, the GRK specificity for beta-arrestin recruitment does not c

281 They also suggest that the GRK/arrestin system, rather than serving as a primary me

282 embranes by intrinsic GRK activity using the GRK phosphosite-specific antibody that recognizes pS(355

283 discuss the GPCR signalling pathways and the GRKs involved in the pathophysiology of heart disease.

284 Characterization of the GRKs participating in the phosphorylation of the beta2-a

285 ated GPCRs dock to an allosteric site on the GRKs and thereby stimulate kinase activity.

286 mined that there is no requirement for these GRK sites in PKA-mediated phosphorylation at high agonis

287 K1 and GRK6, our data suggest that all three GRK subfamilies make conserved interactions with G prote

288 an increase in PKC activity, which leads to GRK-2 translocation and subsequent D1 receptor hyper-ser

289 After U50,488H treatment, GRK-mediated, but not PKC-mediated, KOPR phosphorylation

290 After U50,488H treatment, GRKs, but not PKC, were involved in agonist-induced KOPR

291 en exposed to 1 mum isoproterenol to trigger GRK site-mediated desensitization, only wild-type recept

292 In cardiomyocytes, GRK2 and GRK5 are two GRKs important for myocardial regulation, and both have

293 rhodopsin by 50 to 90% relative to wild-type GRK, as well as autophosphorylation and tubulin phosphor

294 Therefore, our study uncovers GRKs as targets for ameliorating pathological cardiac ef

295 ave been reported, the mechanisms underlying GRK activation are not well-understood, in part because

296 (2)-adrenergic receptor (beta 2AR), in vitro GRK phosphorylation of light-activated rhodopsin, and ba

297 Here we investigate whether GRK or RGS governs the overall rate of recovery of the l

298 our understanding of the mechanism by which GRKs regulate the function of activated GPCRs.

299 While GRKs also interact with and/or phosphorylate many other

300 GF-1R signaling/degradation, consistent with GRK isoform-specific serine phosphorylation.