ライフサイエンスコーパス: GCK

1 ion study (n = 46 (1.3%) MODY (HNF1A, HNF4A, GCK)).

2 f function of the gene encoding glucokinase (GCK).

3 o1, and decreased expression of glucokinase (Gck).

4 ost-translational activation of glucokinase (GCK).

5 f fasting glucose is the enzyme glucokinase (GCK).

6 ting in induction of the enzyme glucokinase (GCK).

7 transfection of Klf6 led to up-regulation of Gck.

8 tion of JNK and p38 by ectopically expressed GCK.

9 nction and unexpected mode of regulation for GCK.

10 etion in beta-cells such as pdx1, slc2a2 and gck.

11 rease in catalytic efficiency over wild-type GCK.

12 d proteinuria and microalbuminuria was rare (GCK, 1% [95% CI, 0.2%-6%]; controls, 2% [95% CI, 0.2%-8%

13 t how two novel cytokinetic ring components, GCK-1 (germinal center kinase-1) and CCM-3 (cerebral cav

14 GCK-1 and CCM-3 are recruited by active RhoA and anillin

15 Together, our results suggest that GCK-1 and CCM-3 regulate cortical actomyosin contractili

16 GCK-1 or CCM-3 depletion also reduced RGA-3 levels in pu

17 ytokinetic furrowing, following depletion of GCK-1 or CCM-3.

18 ogy to mammalian Ste20 family kinases of the GCK-1 subfamily.

19 GCK-1 works together with CCM-3, a known binding partner

20 We identified GCK-1, a conserved serine/threonine kinase [8], as a put

21 ed in HNF-1alpha subjects (29.5%) but not in GCK (18.5%) subjects.

22 Neuropathy was rare in patients with GCK (2% [95% CI, 0.3%-8%]) and controls (95% CI, 0% [0%-

23 ue to alanine rendered CLH-3b insensitive to GCK-3 inhibition.

24 Inhibition is brought about by GCK-3 kinase-mediated phosphorylation of S742 and S747 l

25 Channel inhibition occurs by GCK-3 kinase-mediated phosphorylation of serine residues

26 We also show that GCK-3 modifies Zn(2+) inhibition, which is thought to be

27 ubunit interface changes dramatically during GCK-3-mediated channel inhibition and that these changes

28 ibits channel activity to the same extent as GCK-3.

29 se showed reduced beta-cell function in both GCK (48% controls, P<0.0001) and HNF-1alpha (42% control

30 Germinal center kinase (GCK), a member of the Ste20 family, selectively activate

31 on, we have identified two novel spontaneous GCK-activating mutations whose clinical phenotype clearl

32 est a mechanism for integrative control over GCK activation and, therefore, glucose metabolism and in

33 Posttranslational GCK activation can be stimulated through either G protei

34 rom the endoplasmic reticulum (ER) decouples GCK activation from receptor stimulation.

35 Transient, glucose-stimulated GCK activation was observed in betaTC3 and MIN6 cells.

36 When expressed in islets, fluctuations in GCK activation were observed in response to glucose, and

37 explore the potential for glucose-stimulated GCK activation, the GCK biosensor was optimized using ci

38 etween cytoplasmic Ca(2+) concentrations and GCK activation.

39 Although curcumin suppressed TAK1 and GCK activities at high concentrations, this inhibition c

40 GLP-1 treatment increased GCK activity and enhanced GCK S-nitrosylation in betaTC3

41 WT and P446L-GKRP-mediated inhibition of GCK activity and subsequent regulation by phosphate este

42 Differences in GCK activity between 5- to 6- and 12-week-old rats were

43 red with lean controls; and 3) deficiency in GCK activity does not explain failure of diabetic ZDF is

44 Islet GCK activity for ZDF and ZF rats was 1.7-fold greater th

45 o difference in dose-dependent inhibition of GCK activity or F1P-mediated regulation.

46 regulatory protein gene-leading to increased GCK activity-had reduced numbers of circulating Treg cel

47 gulatory protein, which negatively regulates GCK activity.

48 ns of F6P, resulting indirectly in increased GCK activity.

49 nd insulin, whereas Nkx2.2, Nkx-6.1, Glut-2, Gck, aldo-B, the liver isoform of pyruvate kinase, and i

50 ecreased expression of Nkx-6.1, glucokinase (Gck), aldolase B (aldo-B), and insulin, whereas Nkx2.2,

51 TNF-mediated apoptosis; forced expression of GCK alone or in combination with TRAF2 efficiently incre

52 Recombinant human GCK and both human wild-type (WT) and P446L-GKRP protein

53 Our data suggest that variation in GCK and G6PC2 have additive effects on both fasting gluc

54 g glucose and 30' Deltainsulin stratified by GCK and G6PC2, we noted divergent changes in these quant

55 Two other members of this kinase family, GCK and HPK1, contain C-terminal regulatory domains with

56 GCK and KLF6 mRNAs correlate directly in human NAFLD tis

57 logue germinal center kinase (GCK), and both GCK and MEKK1 associate in vivo with the adapter protein

58 Here we show that endogenous GCK and MEKK1 associate in vivo.

59 Of the members of this family, GCK and MSST1 are most similar to NIK in that they bind

60 GCK and RIP, in turn, signal by binding MAPKKKs upstream

61 ion by binding two proximal protein kinases: GCK and RIP.

62 Common genetic variants in GCK and TCF7L2 are associated with higher fasting glucos

63 Maternal GCK and TCF7L2 variants are associated with glucose leve

64 idity of structural and functional models of GCK and the putative allosteric activator site, which is

65 h which we demonstrate that purified, active GCK and TRAF2 activate MEKK1.

66 of YT2D patients had proteinuria (P<.001 vs GCK) and 21% (95% CI, 13%-32%) had microalbuminuria (P<.

67 Glucokinase (GCK) and glucose-6-phosphatase catalytic subunit 2 (G6PC

68 glucose fluxes revealed reduced glucokinase (GCK) and glycogen synthase fluxes as compared with those

69 imilarities to human germinal center kinase (GCK) and human hematopoietic progenitor kinase 1.

70 r protein that inhibits hepatic glucokinase (GCK) and plays a critical role in glucose homeostasis.

71 the associations between variants rs1799884 (GCK) and rs7903146 (TCF7L2) and OGTT outcomes at 24-32 w

72 encoding the glycolytic enzyme glucokinase (GCK) and the transcription factor hepatocyte nuclear fac

73 20 protein homologue germinal center kinase (GCK), and both GCK and MEKK1 associate in vivo with the

74 lular localization, ability to interact with GCK, and kinetic activity of the encoded proteins.

75 Although the TRAF2 TRAF domain binds ASK1, GCK, and the highly related kinase GCKR, the RING finger

76 tivates a GCK promoter-reporter, identifying GCK as a KLF6 direct transcriptional target.

77 A (mRNA) expression of KLF6 and glucokinase (GCK), as an important mediator of insulin sensitivity, i

78 l for glucose-stimulated GCK activation, the GCK biosensor was optimized using circularly permuted mC

79 ent changes in these quantitative traits for GCK but parallel changes for G6PC2.

80 uted to direct transcriptional regulation of Gck by LRH-1.

81 human SPS1 homologue germinal center kinase (GCK) can interact in vivo with the TNFR1 signal transduc

82 Glucokinase (GCK) catalyzes the rate-limiting step of glucose catabol

83 Rare mutations of GCK cause fasting hyperglycemia and alter birth weight.

84 Mutations in the gene encoding glucokinase (GCK) cause a mild hereditary form of diabetes termed mat

85 Mutations in glucokinase (GCK) cause a spectrum of glycemic disorders.

86 KLF6 regulation of GCK contributes to the development of hepatic insulin re

87 Glucokinase (GCK) controls the rate of glucose metabolism in pancreat

88 Here we explain GCK cooperativity in terms of large-scale, glucose-media

89 t of PAMPs; however, the mechanisms by which GCK couples to downstream events remain unclear.

90 -specific association was also found between GCK CpG4 methylation and total cholesterol (TC) concentr

91 Gender disparity in GCK CpG4 methylation might provide a clue to elaborate t

92 Our results showed that elevated GCK CpG4 methylation might suggest a risk of T2D in Chin

93 Significantly elevated methylation levels of GCK CpG4 methylation were observed in T2D patients than

94 Thus, GCK-dependent glycolysis regulates Treg cell migration.

95 We show that these same PAMPs, in a GCK-dependent manner, activate mixed lineage kinases-2 a

96 ith diabetes in Lithuania was 3.5% (1.9% for GCK diabetes, 0.7% for HNF1A, 0.2% for HNF4A and ABCC8,

97 glucose loads in patients with glucokinase (GCK)-diabetes (MODY2) and hepatocyte nuclear factor 1alp

98 esponse to oral glucose remain unaffected in GCK-diabetes, reflecting important pathogenetic differen

99 e) of hexokinase (HK) and Km of glucokinase (GCK) did not differ between groups.

100 GCK dysfunction leads to several potentially fatal disea

101 ed oligomerization also activates MEKK1, and GCK elicits enhanced oligomerization of coexpressed MEKK

102 pression of Slc2a2 (also known as Glut2) and Gck (encoding glucokinase) in beta-cells, which results

103 lved in mitogenic response, and glucokinase (Gck), encoding a key metabolic enzyme.

104 timated that posttranslational activation of GCK enhances glucose metabolism by approximately 35%.

105 The extent to which common variation of GCK explains normal variation of fasting glucose and bir

106 Absence of Gck expression did not prevent the glucose responsivenes

107 We further established that hepatic Gck expression is decreased in the HIP rat model of T2DM

108 GCK expression was also linked to adverse clinical outco

109 Accordingly, in DeltaKlf6 hepatocytes Gck expression was reduced and stable transfection of Kl

110 ns like C3G, protein kinases of the Abl- and GCK-families and small GTPases like Rap1 and Rac.

111 This is the first time that a GCK family kinase is shown to be potentially involved in

112 the cloning and characterization of a novel GCK family kinase, Traf2- and Nck-interacting kinase (TN

113 ogenous GCKR in primary B cells, implicating GCK family proteins in CD40-mediated B-cell functions.

114 1 is a member of the germinal center kinase (GCK) family that has been implicated in the regulation o

115 The second cluster (MTNR1B, GCK) featured risk alleles associated with reduced insul

116 The almost complete abrogation of GCK flux in G6pc-deficient liver also explains the contr

117 A strong reduction in hepatic GCK flux in L-G6pc-/- mice furthermore limits the phosph

118 so demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes.

119 The GCK gene encodes hexokinase 4, which catalyzes the first

120 tudied mice with genetic inactivation of the Gck gene in Sf1 neurons of the VMN (Sf1Gck(-/-) mice).

121 We conclude that the -30 beta-cell GCK gene promoter variant is associated with reduced bet

122 The presence of the -30 beta-cell GCK gene promoter variant was determined by single-stran

123 At baseline, the -30 beta-cell GCK gene promoter variant was present in 15.4% of subjec

124 ced recruitment of IR and its transducers to Gck gene synchronized with elongating Pol II.

125 f the beta-cell promoter of the glucokinase (GCK) gene observed to be present more frequently in Japa

126 Our results support a model in which GCK generates its cooperative kinetic response at low gl

127 zed in vivo role for germinal center kinase (GCK, genome nomenclature: map4k2), a mammalian Sterile 2

128 ncluding Ins1 (insulin), Slc2a2 (GLUT2), and Gck (glucokinase).

129 several biomarker genes for hepatotoxicity (gck, gsr and nqo1) and caused hepatic vacuolization and

130 Patients with GCK had a low prevalence of clinically significant macro

131 Patients with GCK had a low prevalence of clinically significant micro

132 Thirty percent of patients with GCK had retinopathy (95% CI, 21%-41%) compared with 14%

133 High-resolution NMR investigations of GCK have elucidated millisecond-timescale dynamics under

134 th SNPs in five of the six known MODY genes: GCK, HNF1A, HNF1B, NEUROD1, and HNF4A.

135 s, this activation is mediated solely by the GCK homology region of TNIK.

136 prehensively define the role of variation of GCK in determination of fasting glucose and birth weight

137 a cells revealed low expression of TRAF2 and GCK in early-stage melanoma, which coincided with poor r

138 onfirmed five regions associated with HbA1c (GCK in Europeans and African-Americans, HK1 in Europeans

139 dies confirm falling levels of both KLF6 and GCK in fat-laden hepatocytes.

140 on of the dominant negative form of TRAF2 or GCK in late-stage melanoma cells reduced NF-kappaB activ

141 /K140E)) and with the level of expression of GCK in liver.

142 We find that disruption of gck in mice strongly impairs PAMP-stimulated macrophage

143 Thus Gck in the VMN plays a sex-specific role in the glucose-

144 To test the role of Gck in VMN glucose sensing and physiological regulation,

145 lation of the glycolytic enzyme glucokinase (GCK) in mice.

146 rated in vitro and in vivo that silencing of GCK induces MM cell growth inhibition, associated with b

147 Furthermore, GCK inhibitors might represent an alternative therapy to

148 Agonist activation of GCK involves the TRAF6-dependent transient stabilization

149 mon sequence variation in the genes encoding Gck, Ipf1, Tcf2, and NeuroD1 (MODY2 and MODY4-MODY6, res

150 tudies demonstrate, for the first time, that GCK is a molecular therapeutic target in DLBCL tumors an

151 The defect in GCK is a stable defect of glucose sensing, whereas the H

152 Here, we show that endogenous GCK is activated by polyinosine-polycytidine [poly(IC)]

153 Thus, GCK is an essential PAMP effector coupling JNK and p38,

154 GCK is an exception with near-complete penetrance in all

155 uggest that post-translational activation of GCK is an important mechanism for mediating the insulino

156 GCK is constitutively active, and the kinase activity of

157 We find that the small domain of unliganded GCK is intrinsically disordered and samples a broad conf

158 Gck is known to be the glucose sensor for glucose metabo

159 nt from textbook models of allostery because GCK is monomeric and contains only one glucose-binding s

160 ctivation of MEKK1, but the kinase domain of GCK is not.

161 itutively active, and the kinase activity of GCK is required for GCK ubiquitination.

162 Here we show that GCK is required for JNK and, unexpectedly, p38 activatio

163 RNA interference experiments indicate that GCK is required for the maximal activation of JNK by LPS

164 nhibitors of the proteasome, indicating that GCK is subject to proteasomal turnover.

165 GCK is ubiquitinated in situ and stabilized by inhibitor

166 Glucokinase (Gck) is a critical regulator of glucose-induced insulin

167 Glucokinase (GCK) is a key regulatory enzyme in the pancreatic beta-c

168 ian Ste20 orthologue germinal center kinase (GCK) is required for the activation of JNK by a subset o

169 Human glucokinase (GCK) is the prototypic example of an emerging class of p

170 Finally, we also found that GCK-IV kinase inhibition also prevented the attrition of

171 upled with genome editing, we validated that GCK-IV kinase knockout improves neuronal survival, compa

172 er, these results demonstrate a role for the GCK-IV kinases in dissociating the cell death and axonal

173 ified the role of germinal cell kinase four (GCK-IV) kinases in cell death and additionally revealed

174 ant pedigrees with novel missense mutations (Gck(K140E) and Gck(P417R)) in the gene encoding glucokin

175 pe (mild-to-severe: Gck(+/+) < Gck(P417R/+), Gck(K140E)(/+) < Gck(P417R/P417R), Gck(P417R/K140E), and

176 glucokinase regulatory protein-binding site (GCK(K140E)), but not the ATP binding cassette (GCK(P417R

177 +) < Gck(P417R/P417R), Gck(P417R/K140E), and Gck(K140E/K140E)) and with the level of expression of GC

178 GCK kinetic activity was observed spectrophotometrically

179 GCK knockdown (KD) in MM cells demonstrated in vitro and

180 The novel GCK-like kinase (GLK) has a nucleotide sequence that enc

181 This protein kinase, designated HPK/GCK-like kinase (HGK), has nucleotide sequences that enc

182 The second group is represented by the GCK-like members, which contain an N-terminal catalytic

183 ed serine/threonine kinase, belonging to the GCK-like subfamily.

184 Residues of glucose-free GCK located in the small domain displayed distinct excha

185 corresponded with genotype (mild-to-severe: Gck(+/+) < Gck(P417R/+), Gck(K140E)(/+) < Gck(P417R/P417

186 GCK maintains glucose homeostasis by displaying a sigmoi

187 c target in DLBCL tumors and that inhibiting GCK may significantly extend DLBCL patient survival.

188 f our study is to assess the contribution of GCK methylation to type 2 diabetes (T2D).

189 GCK methylation was evaluated in 48 T2D cases and 48 age

190 As expected, both KATP-GOF and KATP-GOF/GCK+/- mice showed lack of glucose-stimulated insulin se

191 ects with HNF1A-MODY (n = 188), glucokinase (GCK)-MODY (n = 118), hepatocyte nuclear factor 4-alpha (

192 comparing insulin sensitivity in control and GCK-MODY and the contribution of hyperinsulinemia by com

193 ontribution of hyperinsulinemia by comparing GCK-MODY and type 1 diabetes.

194 e disposal similarly in control subjects and GCK-MODY but was 29% and 22% less effective in type 1 di

195 Analysis of four GCK-MODY patients revealed a metabolite pattern similar

196 atic assays and replicated in a cohort of 11 GCK-MODY patients.

197 It has therefore been suggested that GCK-MODY represents a metabolically compensated conditio

198 Our results show that GCK-MODY represents a metabolically normal condition, wh

199 Basal insulin levels in control subjects and GCK-MODY were nearly equal but were 2.5-fold higher in t

200 (hyperinsulinemia and hyperglycemia matching GCK-MODY).

201 acids similarly between control subjects and GCK-MODY, but to a lesser extent for type 1 diabetes.

202 urity-onset diabetes of the young (MODY)2 or GCK-MODY.

203 d similarly elevated for type 1 diabetes and GCK-MODY.

204 kinase-maturity-onset diabetes of the young (GCK-MODY; euinsulinemia and hyperglycemia), and type 1 d

205 rum from patients with MODY1 (HNF4A), MODY2 (GCK), MODY3 (HNF1A), and type 2 diabetes and from health

206 th five types of MODY: MODY1 (HNF4A), MODY2 (GCK), MODY3 (HNF1A), MODY5 (HNF1B), and MODY8 (CEL) with

207 Glucose-feeding increased Gck mRNA expression in livers of lean but not ob/ob mice

208 ng genes that are atRA responsive, Glut2 and Gck mRNA levels were decreased in isolated islets from R

209 ical to that in cells from healthy controls, GCK mutant beta cells required higher glucose levels to

210 urprisingly, extracts from liver of diabetic GCK mutants inhibited activity of the recombinant enzyme

211 ting hyperglycaemia likely to be caused by a GCK mutation and aid identification of probands and fami

212 ipants 35 years or older was conducted in 99 GCK mutation carriers (median age, 48.6 years), 91 nondi

213 and French MODY family members, including 45 GCK mutation carriers and 40 HNF-1alpha mutation carrier

214 s (T2D) and to investigate the proportion of GCK mutation carriers diagnosed with diabetes using HbA1

215 hese are the first two cases of a homozygous GCK mutation diagnosed outside infancy.

216 lso effective in discriminating those with a GCK mutation from those with T1D/T2D.

217 well HbA1c can discriminate patients with a GCK mutation from unaffected family members and young-on

218 48.6 years of hyperglycemia, patients with a GCK mutation had low prevalence of microvascular and mac

219 All patients (123/123) with a GCK mutation were above the lower limit of the HbA1c age

220 Median HbA1c was 6.9% in patients with the GCK mutation, 5.8% in controls, and 7.8% in patients wit

221 crease diabetes diagnosis in patients with a GCK mutation.

222 30 patients with diabetes due to homozygous GCK mutations (19 unique mutations, including 16 missens

223 Individuals with inactivating GCK mutations (n = 129), familial controls (n = 100), T1

224 We report two novel GCK mutations (T65I and W99R) that have arisen de novo i

225 c >/=48 mmol/mol classified more people with GCK mutations as having diabetes than FPG >/=7 mmol/l (6

226 eutic agents and hyperinsulinemia-associated GCK mutations share a strikingly similar activation mech

227 elevated glucose concentrations, carriers of GCK mutations showed lower levels of free fatty acids an

228 hich we predict can be caused by a subset of GCK mutations that cause monogenic diabetes, electrical

229 report the largest case series of homozygous GCK mutations to date and demonstrate that they can caus

230 HbA1c reference ranges in subjects with GCK mutations were: 38-56 mmol/mol (5.6-7.3%) if aged </

231 onal case series of patients with homozygous GCK mutations.

232 with heterozygous, inactivating glucokinase (GCK) mutations have mild fasting hyperglycemia from birt

233 This included simulating GK gene (GCK) mutations that cause monogenic diabetes.

234 l for identifying patients with glucokinase (GCK) mutations which cause lifelong persistent fasting h

235 Neither patients with GCK nor controls required laser therapy for retinopathy

236 xpression and respective activities of TRAF2/GCK occur during melanoma development and regulate its s

237 ease of ER Ca(2+) stimulates activation of a GCK optical biosensor and potentiates glucose metabolism

238 up differences in the kinetic parameters for GCK or in the Km values for HK were not significant.

239 ctivation caused by co-transfection of TAK1, GCK, or HPK1.

240 ith novel missense mutations (Gck(K140E) and Gck(P417R)) in the gene encoding glucokinase (Gck), the

241 K(K140E)), but not the ATP binding cassette (GCK(P417R)), prevented inhibition of enzyme activity by

242 ed with genotype (mild-to-severe: Gck(+/+) < Gck(P417R/+), Gck(K140E)(/+) < Gck(P417R/P417R), Gck(P41

243 P417R/+), Gck(K140E)(/+) < Gck(P417R/P417R), Gck(P417R/K140E), and Gck(K140E/K140E)) and with the lev

244 e: Gck(+/+) < Gck(P417R/+), Gck(K140E)(/+) < Gck(P417R/P417R), Gck(P417R/K140E), and Gck(K140E/K140E)

245 0- to 120-min glucose increment was small in GCK patients (2.4+/-1.8 mmol/l) but large in HNF-1alpha

246 Neither patients with GCK patients nor controls had proteinuria and microalbum

247 The GCK patients showed a similar phenotype between and with

248 AF6-dependent transient stabilization of the GCK polypeptide rather than an increase in intrinsic kin

249 strains JLS, KMS, and MCS, and M. gilvum PYR-GCK), presenting evidence for past horizontal gene trans

250 Subsequently, GCK promoted cytoskeletal rearrangements by associating

251 e utilized to mechanistically link KLF6 with Gck promoter activity.

252 KLF6 binds to the liver-specific Gck promoter and activates a GCK promoter-reporter, iden

253 liver-specific Gck promoter and activates a GCK promoter-reporter, identifying GCK as a KLF6 direct

254 Recombinant mutant GCK proteins were analyzed for kinetic and thermostabili

255 Co-expression of WT or mutant GCK proteins with a sensor for insulin secretory granule

256 arp contrast, in glucose-fed ob/ob mice, the Gck recruitment patterns of active MEK/Erk, IR, and Pol

257 above the upper limit of the age-appropriate GCK reference range.

258 Glucokinase (GCK) regulates glucose storage and disposal in the liver

259 Altered GCK regulation in liver is predicted to enhance glycolyt

260 ilarly, human carriers of a loss-of-function GCK regulatory protein gene-leading to increased GCK act

261 nsive serine/threonine protein kinase termed GCK related (GCKR) that likely signals via mitogen-activ

262 ak interactions with germinal center kinase (GCK)-related kinase (GCKR).

263 Furthermore, GLP-1 activated a FRET-based GCK reporter in living cells.

264 transferase fusion proteins of T65I and W99R GCK revealed that the kinetic changes result in a relati

265 GCK RNA interference and small molecule inhibition induc

266 s780094 [GCKR], rs560887 [G6PC2], rs4607517 [GCK], rs13266634 [SLC30A8], and rs10830963 [MTNR1B]) and

267 GCK rs1799884 and G6PC2 rs560887 have been independently

268 Subjects were genotyped for variants in GCK (rs4607517), G6PC2 (rs560887), ADCY5 (rs11708067), D

269 the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.

270 revealed that blockade of post-translational GCK S-nitrosylation diminished the effects of GLP-1 on g

271 reatment increased GCK activity and enhanced GCK S-nitrosylation in betaTC3 cells.

272 ntury of research, the mechanistic basis for GCK's homotropic allostery remains unresolved.

273 Half-maximal activation of the FRET-GCK sensor was estimated to occur at approximately 400 n

274 ation in cells expressing the optimized FRET-GCK sensor.

275 ntation studies show that hematopoietic cell GCK signaling is essential to systemic inflammation.

276 alysis was TAO3, an STE20-like kinase of the GCK subfamily.

277 s similar to that of control subjects in the GCK subjects (93% controls, P = 0.78) but increased in t

278 Disruption of gck substantially reduces PAMP activation of macrophage

279 Cooperativity in human glucokinase (GCK), the body's primary glucose sensor and a major dete

280 ck(P417R)) in the gene encoding glucokinase (Gck), the mammalian glucose sensor that is mutated in hu

281 s ( approximately 80%) exhibit activation of GCK, this therapy may be applicable to most patients.

282 s, we map the site of disorder in unliganded GCK to a 30-residue active-site loop that closes upon gl

283 ent interaction that stabilizes glucokinase (Gck) to maintain glucose utilization.

284 d the kinase activity of GCK is required for GCK ubiquitination.

285 llosterically regulate the activity of human GCK under physiological conditions.

286 ale dynamics and structural heterogeneity in GCK using a combination of unnatural amino acid incorpor

287 Expression of the GCK(V367M) mutant also blocked GLP-1 potentiation of the

288 The maternal GCK variant was associated with higher fasting glucose i

289 -deficient bacterium, uncovers a hyperactive GCK variant with substantially reduced cooperativity.

290 chanisms, we engineer a fully noncooperative GCK variant, whose functional properties are indistingui

291 iency, fasting glucose levels in carriers of GCK variants and with evolutionary conservation.

292 structural analysis of this loop variant and GCK variants associated with hyperinsulinemic hypoglycem

293 nt positive natural selection on patterns of GCK variation.

294 A 2-fold increase in S-nitrosylated GCK was also observed in mouse islets.

295 approaches with experimental models in which gck was genetically deleted in a population of cells or

296 To determine whether Gck was required for glucose sensing by Sf1 neurons, we

297 and discovered that germinal center kinase (GCK) was extensively activated.

298 ne side chains distributed over all parts of GCK, we show that the origin of kinetic cooperativity is

299 haploinsufficient for beta cell glucokinase (Gck) were unable to increase their beta cell mass in res

300 The hallmark of glucokinase (GCK), which catalyzes the phosphorylation of glucose dur

301 TNF or Fas) and on the availability of TRAF2/GCK, whose expression increases during melanoma progress