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 GRKs utilize a variety of mechanisms to bind tightly, an

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

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

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

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

8 More importantly, such a GRK abnormality took place before cognitive decline and

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

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

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

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

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

14 Although GRK binding to activated GPCRs results in kinase activat

15 not major determinants of selectivity among GRK subfamilies.

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

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

18 isms underlying paroxetine selectivity among GRKs.

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

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

21 - 0.009/min; t(1/2) = 1.6 min), than PKA and GRK site dephosphorylation, respectively, clearly dissoc

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

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

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

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

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

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

35 Although both GRKs also contain putative phosphorylation sites for PKC

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

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

38 GRK 5 and 6, and reciprocally diminished by GRK 2 and 3.

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 phorylation-dependent receptor regulation by GRKs, we have examined M1 mACh receptor signaling in hip

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

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

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

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

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

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

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

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

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

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

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

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

57 nine 180 for uncoupling but that a different GRK and arrestin-dependent mechanism controlled muOR int

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

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

60 n binding, we studied the roles of different GRKs in promoting beta-arrestin-mediated extracellular s

61 This differential GRK activation leads to distinct functional consequences

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

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

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

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

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

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

68 bout the cellular localization of endogenous GRKs.

69 promote this interaction, thereby enhancing GRK activity.

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

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

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

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

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

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 the four widely expressed isoforms of GRKs (GRK 2, 3, 5, and 6) in regulating beta-arrestin-mediated

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

85 The selectivity of balanol among human GRKs is assessed.

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

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

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

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

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

91 kinase activation are intimately coupled in GRKs.

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

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

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

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

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

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

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

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

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

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 Because G protein-coupled receptor kinase (GRK) phosphorylation of such receptors is generally a pr

107 2 and the G protein-coupled receptor kinase (GRK) site phosphoserines 355 and 356 of the beta2-adrene

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

138 G protein-coupled receptor (GPCR) kinases (GRKs) phosphorylate agonist-activated GPCRs, initiating

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

172 G protein-coupled receptor kinases (GRKs) specifically phosphorylate agonist-occupied G prot

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

174 lated by G protein-coupled receptor kinases (GRKs), a process that mediates agonist-specific desensit

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

201 activation is enhanced by overexpression of GRK 5 and 6, and reciprocally diminished by GRK 2 and 3.

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

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

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

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

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

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

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

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

210 ptors phosphorylated by different classes of GRKs.

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

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

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

214 Efforts to study the acute effects of GRKs in intact cells have been limited by a lack of spec

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

216 Interaction of GRKs with activated receptors serves to stimulate their

217 les of the four widely expressed isoforms of GRKs (GRK 2, 3, 5, and 6) in regulating beta-arrestin-me

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

233 om its previously observed position in other GRKs.

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

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

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

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

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

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

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

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

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

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

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

245 Since GRK and arrestins demonstrate no strict receptor specifi

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

247 Slow GRK site dephosphorylation after antagonist treatment wa

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

249 c receptor (alpha(2A)AR) as a model to study GRK/receptor interaction because GRK2 phosphorylation of

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

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

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

253 loop PKA site Ser262 and the putative C-tail GRK sites Ser355, Ser356 of the human beta2AR overexpres

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

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

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

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

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

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

260 These results suggest that GRK-dependent phosphorylation of muOR required threonine

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

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

263 results suggest there is a difference in the GRK requirement for initial ligand-induced internalizati

264 355, 356, and 364 play a pivotal role in the GRK-mediated desensitization, beta-arrestin binding, and

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

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

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

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

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

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

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

272 eased basal levels of phosphorylation of the GRK sites Ser355, Ser356 in both COS-7 and HEK 293 cells

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

300 h mammalian arrestin proteins cooperate with GRKs in receptor desensitization, loss of C. elegans arr