ライフサイエンスコーパス: GRK2

1 ough release of G protein receptor kinase 2 (GRK2).

2 on with G protein-coupled receptor kinase 2 (GRK2).

3 such as G protein-coupled receptor kinase 2 (GRK2).

4 e the specific role of Gq-protein-binding by GRK2.

5 n inhibitor with more modest selectivity for GRK2.

6 expression, and the cognate kinases GRK1 and GRK2.

7 atients were evaluated for I5LO1, PEBP1, and GRK2.

8 endothelin signaling, which is regulated by GRK2.

9 of TGR5 interaction with beta-arrestin 2 and GRK2.

10 -type Ca(2+) channel currents and SR load by GRK2.

11 expression of GRKInh, a peptide inhibitor of GRK2.

12 tor, which is facilitated by the GPCR kinase Grk2.

13 t end, short hairpin RNA was used to inhibit GRK2, 3, 5, and 6 in RBL-2H3 cells stably expressing CXC

14 te whether the fish homologs of GRK2 and -5, Grk2/3 and Grk5, also have unique, complementary, or com

15 he beta2AR in ASM and the ability to exploit GRK2/3 functional domains to render ASM hyporesponsive t

16 ehydrochloride), to study the involvement of GRK2/3 in acute agonist-induced MOPr desensitization.

17 g T370, T376, and T379 specifically requires GRK2/3 isoforms, and the same sequence controls opioid r

18 GRK2/3 knockdown or expression of the GRK2 C terminus ca

19 2/3 were stably expressed, or siRNA-mediated GRK2/3 knockdown was performed, in human ASM cultures, a

20 The Grk2/3 loss-of-function embryos were rescued by this app

21 actile state, we assessed the specificity of GRK2/3 regulation of procontractile and relaxant G-prote

22 A loss of Grk2/3 results in dilated atria and hypoplastic ventricl

23 t although this seems to be the case for the GRK2/3 subfamily, GRK5/6 effectively phosphorylate inact

24 Functional domains of GRK2/3 were stably expressed, or siRNA-mediated GRK2/3 k

25 In the case of Grk2/3, the progenitor decrease was confined to a subset

26 o clarify the potential utility of targeting GRK2/3-mediated desensitization as a means of manipulati

27 dels is G protein-coupled receptor kinase-2 (GRK2), a kinase originally discovered to be involved in

28 GRK2, a G protein-coupled receptor kinase, plays a criti

29 1 week post-I/R in cardiomyocyte-restricted GRK2 ablated mice (also post-I/R) still demonstrated sig

30 In isolated muscle mechanics testing, GRK2 ablation caused a significant decrease in the speci

31 bryos with systemic or endothelium-selective Grk2 ablation had marked vascular malformations involvin

32 rdiomyocytes from mice with cardiac-specific GRK2 ablation normalized the TNFalpha-mediated loss in c

33 th activated fibroblast- or myocyte-specific GRK2 ablation-each initiated after myocardial ischemia-r

34 These two classes of compounds bind to the GRK2 active site in a similar configuration but contain

35 As such, levels of GRK2 activity in the heart directly correlate with cardi

36 energic receptors are the primary target for GRK2 activity in the heart; phosphorylation by GRK2 lead

37 RV GRK2 activity increased in parallel with a reduction in

38 equently, therapeutic strategies that target GRK2 activity, not expression, may be more effective for

39 Furthermore, increased expression of GRK2 after cardiac insult exacerbates injury and speeds

40 be partially rescued by the deletion of one Grk2 allele.

41 GRK2 and -5 belong to different subfamilies and function

42 to investigate whether the fish homologs of GRK2 and -5, Grk2/3 and Grk5, also have unique, compleme

43 milarly, we demonstrated opposing effects of GRK2 and -6 on IGF-1R degradation: GRK2 decreases wherea

44 were knocked down using siRNA, but not when GRK2 and Arrestin2 were knocked down.

45 inhibitor, was identified as an inhibitor of GRK2 and co-crystallized in the active site.

46 neutrophil migration through upregulation of GRK2 and downregulation of surface CXCR2 expression.

47 t therapies targeted at balancing nociceptor GRK2 and EPAC1 levels have promise for the prevention an

48 Conversely, the dual-specific GRK2 and ERK cascade inhibitor, RKIP (Raf kinase inhibit

49 hibitor, 14as, with an IC50 of 30 nM against GRK2 and greater than 230-fold selectivity over other GR

50 brane-permeable, small-molecule inhibitor of GRK2 and GRK3, Takeda compound 101 (Cmpd101; 3-[[[4-meth

51 exhibited nanomolar IC50 values against both GRK2 and GRK5 and good selectivity against other closely

52 GRK2 and GRK5 are overexpressed in the failing heart and

53 We show that GRK isoforms GRK2 and GRK5 are similarly expressed in direct and indi

54 In summary, we found that GRK2 and GRK5 control cardiac function as well as morpho

55 Moreover, these MR-dependent GRK2 and GRK5 non-canonical activities appear to involve

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

57 ween phosphorylation of the same receptor by GRK2 and GRK5, demonstrating preference for the latter.

58 Both GRK2 and GRK5, the predominant GRKs expressed in the hea

59 GRK2 and GRK6 coimmunoprecipitate with IGF-1R and increa

60 Inhibition of GRK2 and GRK6 increased CXCR1 and CXCR2 resistance to ph

61 ity of the G protein-coupled receptor kinase GRK2 and inhibited neutrophil migration, whereas the MAP

62 nduced betaAR desensitization is mediated by GRK2 and is independent of Gbetagamma, uncovering a hith

63 flox)/cre recombinase) and overexpression of GRK2 and its regulator of G protein signaling homology (

64 MAPK pathway because dual inhibition of the GRK2 and RAF-MAPK axis by the Raf kinase inhibitor prote

65 estin/IGF-1R association to be transient for GRK2 and stable for GRK6.

66 th a prolongation of the interaction between GRK2 and the M3-ACh receptor and enhanced arrestin recru

67 Our data demonstrate a role for GRK2 (and potentially also GRK3) in agonist-induced MOPr

68 G protein-coupled receptor kinases 2 (GRK2) and 5 (GRK5) are fundamental regulators of cardiac

69 ch involves 15LO1/PEBP1 interactions to free GRK2, and allows it to phosphorylate (and desensitize) b

70 protection against H/R was elicited only via GRK2- and beta-arrestin1-dependent signaling.

71 Cholinergic interneurons are enriched in GRK2, arrestin-3, and GRK5.

72 l muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeleta

73 Thus, we identify GRK2 as a potential molecular link between inflammation

74 eral of the hallmarks of cancer puts forward GRK2 as an oncomodifier, able to modulate carcinogenesis

75 ntified G protein-coupled receptor kinase 2 (GRK2) as a key angiogenesis regulator.

76 dentify G protein-coupled receptor kinase 2 (GRK2) as a kinase that can phosphorylate CLCb on Ser204.

77 GRK2 associated with PEBP1 after 10 minutes of ISO in as

78 ed PKA scaffolding significantly reduces DOR-GRK2 association at the plasma membrane and consequently

79 into SECs isolated from Cav1-deficient mice, GRK2 association with CAV1 was evident, whereas transduc

80 r, the mechanism that maintains constitutive GRK2 association with DOR is unknown.

81 Protein kinase A (PKA) phosphorylation of GRK2 at Ser-685 targets it to the plasma membrane.

82 es demonstrated that both Galpha(q)/PKC- and GRK2/beta-arrestin1-dependent V(1A)R signaling were capa

83 c2 cells mediates protective signaling via a GRK2/beta-arrestin1/ERK1/2-dependent mechanism that lead

84 c RKIP mutant displayed a higher affinity to GRK2, but a lower affinity to Raf1.

85 ath, whereas dual inhibition of RAF/MAPK and GRK2 by RKIP induced cardiomyocyte apoptosis, cardiac dy

86 Inhibition of GRK2 by the dominant-negative GRK2-K220R did not affect

87 GRK2/3 knockdown or expression of the GRK2 C terminus caused a significant ( approximately 30-

88 Finally, transgenic expression of the GRK2 C terminus in murine ASM enabled approximately 30-5

89 traction of murine tracheal rings expressing GRK2 C terminus was also assessed.

90 GRK2 C-terminal expression did not affect signaling by m

91 Under conditions of GRK2 C-terminal expression, beta-agonist inhibition of m

92 maleimide, HCl, bisindolylmaleimide X, HCl), GRK2 [C-terminal GRK2 peptide overexpression and small i

93 Higher levels of GRK2 can impair beta-adrenergic receptor-mediated inotro

94 , it has been demonstrated that GRK5, unlike GRK2, can reside in the nucleus of myocytes and exert G

95 ased in injured SECs, resulting in increased GRK2-CAV1 interaction and decreased eNOS activity.

96 phorylation facilitates CAV1 scaffolding and GRK2-CAV1 interaction, thus clustering eNOS within a com

97 istinct conformation of the kinase domain of GRK2 compared with previous complexes with paroxetine an

98 l structure of this compound in complex with GRK2 confirmed the predicted interactions.

99 of connections with other cellular proteins, GRK2 contributes to the modulation of basic cellular fun

100 The up- or down-regulation of GRK2 correlates with several pathological disorders.

101 tion of G-protein-coupled receptor kinase 2 (GRK2) could counteract the disturbed substrate metabolis

102 ith reduced binding affinity toward Galphaq [GRK2(D110A)] and Gbetagamma [GRK2(R587Q)] were used to d

103 ion of the Galphaq coupling-deficient mutant GRK2-D110A suppressed ETA-WT signaling but failed to dec

104 eceptors, whereas the kinase-inactive mutant GRK2-D110A/K220R failed to inhibit signaling of ETA-WT a

105 ffects of GRK2 and -6 on IGF-1R degradation: GRK2 decreases whereas GRK6 enhances ligand-induced degr

106 In contrast, we found that GRK2 deficiency in cholinergic neurons does not alter co

107 Mice with GRK2 deficiency in D2R-expressing neurons also exhibited

108 Here we show that select GRK2-deficient mice display hyperactivity, hyposensitivi

109 t TNFalpha-induced betaAR desensitization is GRK2 dependent.

110 ocytosis of those GPCRs whose endocytosis is GRK2-dependent.

111 n of the GRK2 N terminus or kinase-dead holo-GRK2 diminished ( approximately 30-70%) both PI hydrolys

112 and dominant-negative approaches reveal that GRK2 directly phosphorylates and activates Mst2.

113 Moreover, decreased endothelial Grk2 dosage accelerated tumor growth in mice, along with

114 Our study suggests that GRK2 downregulation is a relevant event in the tumoral a

115 induced G protein-coupled receptor kinase 2 (GRK2) downregulation and genetic deletion of GRK2 mimick

116 f atypical protein kinase C zeta, leading to GRK2-driven Galphas inactivation.

117 to favor vasoconstriction in the absence of GRK2 expression and that this leads to the age-dependent

118 We found that silencing GRK2 expression caused ~50% decrease in antigen-induced

119 GRK2 expression is increased in hypertension and this fa

120 exercise capacity was not altered in MLC-Cre:GRK2(fl/fl) mice compared with wild-type controls.

121 onist, was significantly enhanced in MLC-Cre:GRK2(fl/fl) mice; mechanistically, this seems to be due

122 -specific GRK2 knock-out (KO) mouse (MLC-Cre:GRK2(fl/fl)) to gain a better understanding of the role

123 mediated GRK2 knockdown, GRK2 gene deletion (GRK2(flox/flox)/cre recombinase) and overexpression of G

124 (Gbeta) bind to DDB1 and that Gbeta2 targets GRK2 for ubiquitylation by the DDB1-CUL4A-ROC1 ubiquitin

125 facilitated neutrophil migration by blocking GRK2 function.

126 1, CCG257284, and CCG258748) in complex with GRK2-Gbetagamma Comparison of these structures with thos

127 ed lentiviral shRNA-mediated GRK2 knockdown, GRK2 gene deletion (GRK2(flox/flox)/cre recombinase) and

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

129 Inducible ablation of GRK2 in activated fibroblasts (i.e., myofibroblasts) pos

130 further protection in mice with ablation of GRK2 in activated fibroblasts alone.

131 d, focusing on recently discovered roles for GRK2 in cardiomyocyte metabolism and the effects that th

132 Recently, nonclassical roles for GRK2 in cardiovascular disease have been described, incl

133 gene knockout approach to selectively delete GRK2 in DA D1 receptor (D1R)-, DA D2 receptor (D2R)-, ad

134 s transformed environment promoted decreased GRK2 in ECs and human breast cancer vessels.

135 osphorylatively modified and desensitized by GRK2 in failing cardiomyocytes, contributing to post-MI

136 tization was unaffected, implying a role for GRK2 in MOPr desensitization.

137 relatively little is known about the role of GRK2 in skeletal muscle function and disease.

138 provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role

139 o gain a better understanding of the role of GRK2 in skeletal muscle physiology.

140 To elucidate the specific role of GRK2 in the brain dopamine (DA) system, we used a condit

141 Here we report the localization of GRK2 in the mouse brain and generate novel conditional k

142 indings reveal a cell-type-specific role for GRK2 in the regulation of normal motor behavior, sensiti

143 tion of G-protein coupled receptor kinase 2 (GRK2) in both mouse models.

144 n mice, reduced expression of GPCR kinase 2 (GRK2) in nociceptors promotes cAMP signaling to the guan

145 We suggest that a surface of GRK2, including Leu(4), Val(7), Leu(8), Val(11), and Ser

146 investigated the hypothesis that Gbetagamma-GRK2 inhibition and/or ablation after myocardial injury

147 ntributed to the cardioprotective profile of GRK2 inhibition by preventing cardiomyocyte death, where

148 he potential therapeutic role for Gbetagamma-GRK2 inhibition in limiting pathological myofibroblast a

149 anding of the therapeutic role of Gbetagamma-GRK2 inhibition in treating HF and the potential therape

150 GF1-mediated ERK and AKT activation, whereas GRK2 inhibition increases ERK activation and partially i

151 Systemic small molecule Gbetagamma-GRK2 inhibition initiated 1 week post-I/R in cardiomyocy

152 Systemic small molecule Gbetagamma-GRK2 inhibition initiated 1 week post-I/R provided littl

153 Small molecule Gbetagamma-GRK2 inhibition initiated 1 week post-injury was cardiop

154 Thus, GRK2 inhibition is a novel approach that targets the dys

155 Thus, cardioprotective signaling induced by GRK2 inhibition is overlapping with tumor growth promoti

156 h and development, we analyzed the impact of GRK2 inhibition on cell growth and proliferation.

157 Cardioprotective GRK2 inhibition required an intact ERK axis, which blunt

158 Finally, Gbetagamma-GRK2 inhibition significantly attenuated activation char

159 The enhanced tumor growth upon GRK2 inhibition was attributed to the growth-promoting M

160 eutic potential of small molecule Gbetagamma-GRK2 inhibition, alone or in combination with activated

161 translates into decreased Raf1 and increased GRK2 inhibition.

162 this series is a highly potent and selective GRK2 inhibitor, 14as, with an IC50 of 30 nM against GRK2

163 laid with the binding pose of a known potent GRK2 inhibitor, Takeda103A, a library of hybrid inhibito

164 , paroxetine, was previously identified as a GRK2 inhibitor.

165 vide insight into the further development of GRK2 inhibitors as drug candidates.

166 rticle reviews the most potent and selective GRK2 inhibitors that have been developed.

167 photorelaxation, which is greatly reduced by GRK2 inhibitors.

168 ase-dead mutant in vivo, we demonstrate that GRK2 inhibits CFA-induced hyperalgesia in a kinase activ

169 Finally, we show that GRK2 inhibits Epac1-mediated sensitization of the mechan

170 In vitro, GRK2 inhibits Epac1-to-Rap1 signaling by phosphorylation

171 Of interest, knockdown of GRK2 inhibits epidermal growth factor receptor (EGFR)-me

172 l-induced GRK2 phosphorylation enhanced CAV1-GRK2 interaction and reduced eNOS activity.

173 Inhibiting Gbetagamma-GRK2 interactions has therapeutic benefit in RVH.

174 GRK2 is a G protein-coupled receptor kinase (GRK) that i

175 Because GRK2 is also indispensable for growth and development, w

176 Here we demonstrate that GRK2 is also localized to centrosomes, although it has n

177 omain, indicating that CAV1 interaction with GRK2 is inversely regulated by endothelin-1 and CAV1 sca

178 Collectively these findings demonstrate that GRK2 is localized to centrosomes and plays a central rol

179 orepinephrine concentration, suggesting that GRK2 is recruited to Gbetagamma and alpha(2A)AR with EC5

180 G-protein-coupled receptor kinase 2 (GRK2) is a G-protein-coupled receptor kinase that is ubi

181 G-protein-coupled receptor kinase 2 (GRK2) is a serine/threonine kinase with an important fun

182 tion of G-protein-coupled receptor kinase 2 (GRK2) is an emerging treatment option for heart failure.

183 G-protein-coupled receptor kinase 2 (GRK2) is arising as one of such nodes.

184 lthough G-protein-coupled receptor kinase 2 (GRK2) is the most widely studied member of a family of k

185 cardial G protein-coupled receptor kinase-2 (GRK2) is upregulated in HF patients, causing dysfunction

186 Inhibition of GRK2 by the dominant-negative GRK2-K220R did not affect the proliferation of cultured

187 immunodeficient mice, the dominant-negative GRK2-K220R or a GRK2-specific peptide inhibitor increase

188 optimized interactions with the hinge of the GRK2 kinase domain.

189 e generated a novel skeletal muscle-specific GRK2 knock-out (KO) mouse (MLC-Cre:GRK2(fl/fl)) to gain

190 Finally, cardiac-specific GRK2 knockdown restored the cardioprotective effect of a

191 utilized included lentiviral shRNA-mediated GRK2 knockdown, GRK2 gene deletion (GRK2(flox/flox)/cre

192 n isolated cardiomyocytes from wild-type and GRK2 knockout (GRK2KO) mice without (sham) or with myoca

193 postnatal retinas from endothelium-specific Grk2 knockout animals.

194 m in vivo is completely prevented in cardiac Grk2 knockout mice (KO) and to a lesser extent in Grk5 K

195 Cardiac-specific GRK2 knockout virtually abolished post-MI AdipoR1 phosph

196 ulated pro-hypertrophic Akt signaling in the GRK2 KO skeletal muscle.

197 ggest that the selectivity of paroxetine for GRK2 largely reflects its lower affinity for adenine nuc

198 K2 activity in the heart; phosphorylation by GRK2 leads to desensitization of these receptors.

199 Increased GRK2 levels also correlate with the degree of cognitive

200 Moreover, altered GRK2 levels are starting to be reported in different tum

201 Importantly, myocardial GRK2 levels correlate with levels found in peripheral ly

202 his study was to evaluate whether lymphocyte GRK2 levels predict clinical outcome in HF patients.

203 GRK2 levels showed an additional prognostic and clinical

204 e independent prognostic value of lymphocyte GRK2 levels was also confirmed for all-cause mortality.

205 epinephrine, serum NT-proBNP, and lymphocyte GRK2 levels, as well as clinical and instrumental variab

206 tivation status in heart failure influencing GRK2 levels.

207 haq enhances the extent and stability of the GRK2-M3-ACh receptor interaction, and that not only Gbet

208 These new roles of GRK2 suggest that GRK2 may be a nodal link in the myocyte, influencing bot

209 The independent prognostic value of blood GRK2 measurements in HF patients has never been investig

210 ed that G protein-coupled receptor kinase-2 (GRK2)-mediated uncoupling of beta-adrenergic receptor si

211 ition of phosphoinositide 3-kinase abolished GRK2-mediated betaAR phosphorylation and GRK2 recruitmen

212 nsitization involves at least two autonomous GRK2-mediated components: 1) a phosphorylation-independe

213 he failure of neutrophil migration, impaired GRK2-mediated CXCR2 downregulation, and decreased the ge

214 GRK2-mediated desensitization-downregulation of adrenerg

215 /11 signaling, as the consequence of reduced GRK2-mediated desensitization.

216 Therefore, we sought to determine whether GRK2-mediated DOR desensitization is directed by PKA via

217 This EGFR/GRK2-mediated process depends on the protein kinases mam

218 a-Adrenergic receptor kinase 1 (betaARK 1 or GRK2) mediates desensitization of photorelaxation, which

219 GRK2) downregulation and genetic deletion of GRK2 mimicked the sensitizing effect of inflammation on

220 These data demonstrate that GRK2 modulates FcinRI signaling in mast cells via at lea

221 Targeted mutation of S1248 recapitulates GRK2 modulation, whereas S1291 mutation resembles GRK6 e

222 Inhibition of GRKs by using heparin or GRK2-mutant mice did not block desensitization or alter

223 GRK2 mutants with reduced binding affinity toward Galpha

224 Expression of the GRK2 N terminus or kinase-dead holo-GRK2 diminished ( ap

225 GRK2 null animals exhibit embryonic lethality due to a s

226 compound, 12n (CCG-224406), had an IC50 for GRK2 of 130 nM, >700-fold selectivity over other GRK sub

227 The effect of GRK2 on cytokine generation does not require its catalyt

228 Here, we sought to determine the role of GRK2 on FcinRI signaling and mediator release in mast ce

229 inflammatory pain, we found that increasing GRK2 or decreasing EPAC1 inhibited chronic hyperalgesia.

230 GRK2 or GRK2-RH had no effect on antigen-induced phospho

231 vessels was observed in mice hemizygous for Grk2 or in animals with endothelium-specific Grk2 silenc

232 Here we hypothesized that reduction of GRK2 or increased EPAC1 in dorsal root ganglion (DRG) ne

233 ng sensory neuron-specific overexpression of GRK2 or its kinase-dead mutant in vivo, we demonstrate t

234 Overexpression of GRK2 or its RH domain (GRK2-RH) enhanced antigen-induced

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

236 Moreover, GRK2 overexpression enhanced CXCR4 internalization, via

237 poR1 phosphorylation, whereas virus-mediated GRK2 overexpression significantly phosphorylated AdipoR1

238 Interactions of GRK2, PEBP1, and 15LO1 were detected by means of immunop

239 isindolylmaleimide X, HCl), GRK2 [C-terminal GRK2 peptide overexpression and small interfering RNA (s

240 f ISO in association with low phosphorylated GRK2 (pGRK2) levels.

241 Finally, isoproterenol-induced GRK2 phosphorylation enhanced CAV1-GRK2 interaction and

242 erminal intracellular AdipoR1 region) as the GRK2 phosphorylation sites.

243 s were measured using ELISA, and beta2AR and GRK2 phosphorylation was measured using Western blotting

244 alone paralleled by increases in beta2AR and GRK2 phosphorylation.

245 via the G-protein-coupled receptor kinase 2 (GRK2)/PI3K signaling pathway.

246 ed alveolar epithelial fluid transport via a GRK2/PI3K-dependent mechanism.

247 ated alveolar epithelial fluid transport via GRK2/PI3K-dependent mechanisms.

248 activity, GRK2 Ser-685 phosphorylation, and GRK2 plasma membrane targeting than controls.

249 GRK2 plays an important role in the maintenance of heart

250 ondrial G protein-coupled receptor kinase 2 (GRK2) pro-death activity and GRK5 pro-hypertrophic actio

251 Lymphocyte GRK2 protein levels can independently predict prognosis

252 ro brain natriuretic peptide, and lymphocyte GRK2 protein levels were independent predictors of CV mo

253 ociation from Gbeta2, leading to increase of GRK2 protein.

254 toward Galphaq [GRK2(D110A)] and Gbetagamma [GRK2(R587Q)] were used to determine the specific role of

255 hed GRK2-mediated betaAR phosphorylation and GRK2 recruitment on TNFalpha.

256 tization or cardiac dysfunction showing that GRK2 recruitment to the betaAR is Gbetagamma independent

257 species and ages and that group I mGluRs and GRK2 represent new avenues for neuroprotection in perina

258 Small interfering RNA knockdown of GRK2 resulted in the loss of TNFalpha-mediated betaAR ph

259 lls via at least two mechanisms.One involves GRK2-RH and modulates tyrosine phosphorylation of Syk, a

260 GRK2 or GRK2-RH had no effect on antigen-induced phosphorylation

261 Overexpression of GRK2 or its RH domain (GRK2-RH) enhanced antigen-induced mast cell degranulatio

262 of G protein signaling homology (RH) domain (GRK2-RH).

263 Previously, we discovered two classes of GRK2-selective inhibitors, one stemming from GSK180736A,

264 Site-directed mutagenesis revealed that GRK2 Ser-685 phosphorylation drives the association of G

265 m AKAP-knock-out mice had less PKA activity, GRK2 Ser-685 phosphorylation, and GRK2 plasma membrane t

266 Grk2 or in animals with endothelium-specific Grk2 silencing.

267 Only clathrin recognizes and stabilizes GRK2-specific beta-arrestin-1 conformations.

268 mice, the dominant-negative GRK2-K220R or a GRK2-specific peptide inhibitor increased tumor mass.

269 In the course of a GRK2 structure-based drug design campaign, one inhibitor

270 These new roles of GRK2 suggest that GRK2 may be a nodal link in the myocyt

271 ted by cAMP 1 (EPAC1) by G protein kinase 2 (GRK2) suppresses Epac1-to-Rap1 signaling, thereby inhibi

272 n this respect, GRK4alpha is more similar to GRK2 than GRK6.

273 on with G-protein-coupled receptor kinase-2 (GRK2) that also post-translationally modifies eNOS.

274 itor of G protein-coupled receptor kinase 2 (GRK2) that improves cardiac performance in live animals.

275 ole for G-protein-coupled receptor kinase 2 (GRK2) that renders DOR analgesically incompetent at the

276 er-based assay to monitor the recruitment of GRK2 to activated alpha(2A)-adrenergic receptors (alpha(

277 The recruitment of GRK2 to activated receptors is well known to be mediated

278 re additionally crystallized in complex with GRK2 to give insights into the structural determinants o

279 of the new inhibitors were crystallized with GRK2 to give molecular insights into the binding and kin

280 role of Galphaq in efficient recruitment of GRK2 to M3-ACh receptors.

281 ma membrane targeting and phosphorylation of GRK2 to maintain DOR analgesic incompetence in periphera

282 e of IL-13 plus ISO (10 minutes), binding of GRK2 to PEBP1 decreased, whereas 15LO1 binding and pGRK2

283 The prognostic value of GRK2 to predict cardiovascular (CV) death and all-cause

284 only Gbetagamma but also Galphaq can target GRK2 to the membrane.

285 GRK2 up-regulation can lead to changes in the insulin si

286 GRK2 up-regulation can worsen cardiac ischemia; furtherm

287 s showed significant betaAR desensitization, GRK2 upregulation, and recruitment to the betaAR complex

288 demonstrate here, that genetic knockdown of GRK2 using a small hairpin (sh) RNA results in altered v

289 High level transfection of GRK2 variants influenced signaling of ETA-WT and ETA-6PD

290 etine exhibits up to 50-fold selectivity for GRK2 versus other GRKs.

291 When either GRK2 was increased in vivo by viral-based gene transfer

292 urthermore, interactions between Galphaq and GRK2 were associated with a prolongation of the interact

293 CXCR1 predominantly couples to GRK2, whereas CXCR2 interacts with GRK6 to negatively re

294 n induced a sustained decrease in nociceptor GRK2, whereas priming with the PKCepsilon agonist Psieps

295 review, classical and nonclassical roles for GRK2 will be discussed, focusing on recently discovered

296 off-pathway conformational states unique to GRK2 will likely be key for the development of even more

297 ss the role of Galphaq on the interaction of GRK2 with activated Gq-protein-coupled receptors.

298 85 phosphorylation drives the association of GRK2 with plasma membrane-associated DOR.

299 ET)-based assays to study the interaction of GRK2 with the M3-acetylcholine (M3-ACh) receptor as well

300 In contrast, GRK2-WT acted on both receptors, whereas the kinase-inac