ライフサイエンスコーパス: NHE3

1 ansporters including Na(+)/H(+) exchanger 3 (NHE3).

2 show that glucose exerts a bimodal effect on NHE3.

3 the hormonal stimuli-mediated regulation of NHE3.

4 by interfering with the actions of NHE1 and NHE3.

5 HE3 aa 690 and of the CaMKII-binding site on NHE3.

6 through increased activity of both NHE1 and NHE3.

7 C-5 plays an essential role in exocytosis of NHE3.

8 transport by redistributing Na/K-ATPase and NHE3.

9 isms by which ClC-5 regulates trafficking of NHE3.

10 and caused redistribution of Na/K-ATPase and NHE3.

11 t increase in co-precipitation of ezrin with NHE3.

12 on of NaCl by targeting Na(+)/H(+) exchanger NHE3.

13 ith PI(4,5)P(2) and PI(3,4,5)P(3) binding of NHE3.

14 on of IRBIT enhanced the effect of ANG II on NHE3.

15 order NHE3 and association between ezrin and NHE3.

16 with PI(4,5)P(2) or PI(3,4,5)P(3) binding of NHE3.

17 orylated prevented the downstream effects on NHE3.

18 interaction of ezrin with NHERF1, IRBIT, and NHE3.

19 hich are necessary for cGMP/cGKII to inhibit NHE3.

20 3, which was associated with reduced surface NHE3.

21 present at the same time for cGMP to inhibit NHE3.

22 ion was not necessary for cAMP inhibition of NHE3.

23 cle), resulting in increased ubiquitinylated NHE3 (+140+/-10%); and decreased NHE3 expression (-50+/-

24 (+250+/-30%, vs. controls), decreased total NHE3 (-23+/-2%), and lowered blood pressure (-24+/-2 mm

25 RNA (3 mug/d, 7 d) increased ubiquitinylated NHE3 (+250+/-30%, vs. controls), decreased total NHE3 (-

26 This study identifies recessive mutations in NHE3, a downstream target of GC-C, as a cause of CSD and

27 f NHE3 by effects requiring aa downstream of NHE3 aa 690 and of the CaMKII-binding site on NHE3.

28 Amino acids downstream of NHE3 aa 690 are required for CaMKII to inhibit basal NHE

29 hese results demonstrate that CHP1 increases NHE3 abundance and constitutive function in a manner dep

30 he small intestinal BB Na(+)/H(+) antiporter NHE3 accounts for the majority of intestinal sodium and

31 al brush border (BB) Na(+)/H(+) exchanger 3 (NHE3) accounts for most renal and intestinal Na(+) absor

32 investigated the role of IRBIT in mediating NHE3 activation by ANG II.

33 e endosomal localization of SGK3 and delayed NHE3 activation.

34 trafficking to the BBM and insulin-dependent NHE3 activation.

35 alpha-MD-G normalized NHE3 activity after cholera toxin-induced diarrhea.

36 One complex stimulates basal NHE3 activity and contains ezrin and phosphoinositides a

37 ion of lysophosphatidic acid (LPA) increased NHE3 activity and fluid absorption in diabetic mice via

38 abetic mice with insulin restored intestinal NHE3 activity and fluid absorption.

39 Dexamethasone (4 h) stimulated wild type NHE3 activity and increased surface expression but faile

40 5 min of ANG II treatment for an increase in NHE3 activity and NHE3 surface expression.

41 these (S515A, S515D, or S526A) reduced basal NHE3 activity and surface expression and had no Akti inh

42 omain of SNX27 is required to maintain basal NHE3 activity and surface expression of NHE3 in polarize

43 A GSK-3 inhibitor reduced basal NHE3 activity as well as ezrin-NHE3 binding, and this ef

44 CaMKII inhibits basal NHE3 activity associated with phosphorylation of NHE3 by

45 t NHERF3 reconstitutes calcium inhibition of NHE3 activity by anchoring NHE3 basally and releasing it

46 NHE3, as well as necessary for inhibition of NHE3 activity by calcium ionophore 4-Br-A23187.

47 es, which are required for the inhibition of NHE3 activity by carbachol.

48 WT mice, whereas the degree of inhibition of NHE3 activity by increasing cellular concentration of cA

49 t component; 2) reduced acute stimulation of NHE3 activity by LPA/LPA5R stimulation; and 3) reduced a

50 SLC9A3 missense mutations compromised NHE3 activity by reducing basal surface expression and/o

51 S526D had NHE3 activity equal to wild type with normal Akti inhibi

52 was necessary for LPA-induced stimulation of NHE3 activity in colonic epithelial cells.

53 The role of CK2 in regulation of NHE3 activity in polarized Caco-2/bbe cells was further

54 First, NHE3 activity in proximal tubules of wild type (WT) and

55 he effect of SGLT-mediated glucose uptake on NHE3 activity in the renal proximal tubule.

56 -mediated Na-glucose co-transport stimulates NHE3 activity in vivo by an Akt- and NHERF2-dependent si

57 tides as major components; how it stimulates NHE3 activity is not known.

58 Basal and dexamethasone-stimulated NHE3 activity of Clcn5 KO mice was decreased compared wi

59 In this study, the roles in regulation of NHE3 activity of these two PBMs were investigated, revea

60 d surface expression but failed to stimulate NHE3 activity or increase surface expression when NHE3 w

61 ependent protein kinase II (CaMKII) inhibits NHE3 activity under basal conditions in intact intestine

62 alpha-MD-G-stimulated jejunal NHE3 activity was defective in NHERF2-/- mice and cells

63 NHE3 activity was measured with 2',7'-bis(carboxyethyl)-

64 NHE3 activity was reduced by an Akti.

65 oses an intracellular pH (pHi) dependence of NHE3 activity, although the biophysical and molecular ba

66 and ERK1/2, reduced Na/K-ATPase activity and NHE3 activity, and caused redistribution of Na/K-ATPase

67 690 are required for CaMKII to inhibit basal NHE3 activity, and mutations of the three putative CaMKI

68 cells expressing NHE3, CaMKII inhibits basal NHE3 activity, because the CaMKII-specific inhibitors KN

69 mulation; and 3) reduced acute inhibition of NHE3 activity-specifically, elevated Ca(2+) related (car

70 e changes in NHE3 activity: 1) reduced basal NHE3 activity-specifically, inhibition of the PI3K/AKT-d

71 m site (S719) that accounts for 40% of basal NHE3 activity.

72 sociation of ezrin with NHE3 to affect basal NHE3 activity.

73 ERF3 heterodimerization in the regulation of NHE3 activity.

74 f aa 690 each prevented KN-93 stimulation of NHE3 activity.

75 pecific inhibitors KN-93 and KN-62 stimulate NHE3 activity.

76 ations in either significantly reduced basal NHE3 activity.

77 4,5)P(2) and PI(3,4,5)P(3) binding and basal NHE3 activity.

78 d binding of IRBIT to NHE3 and its effect on NHE3 activity.

79 S719A but not -S719D had multiple changes in NHE3 activity: 1) reduced basal NHE3 activity-specifical

80 s) toward the acidic side in comparison with NHE3 alone, as measured by oscillating pH electrodes com

81 ccupied by NHERF3 and another ligand such as NHE3, alpha-actinin-4, and PKCalpha, promoting formation

82 CHP1 binding to NHE3 also affected its acute regulation.

83 In contrast, expression of Slc9A (NHE3), an electroneutral ion channel, and of GlyR, an in

84 It is associated with increased brush-border NHE3 and association between ezrin and NHE3.

85 F2 and in Caco-2/Bbe cells overexpressing HA-NHE3 and cGKII, and in mouse ileum.

86 Mutations were made in the F1 region of NHE3 and cloned in pet30a and pcDNA3.1 vectors.

87 LPA stimulated NHE3 and fluid absorption in part by increasing NHE3 pro

88 ediated by the Na(+)/H(+) hydrogen exchanger NHE3 and is increased by Na(+)-glucose co-transport in v

89 er-74 of IRBIT decreased binding of IRBIT to NHE3 and its effect on NHE3 activity.

90 pamycin inhibition of mTOR reduces levels of NHE3 and Na(+)/H(+) exchange activity in intestinal tiss

91 leton plays an important role in FSS-induced NHE3 and Na/K-ATPase trafficking, and an intact microtub

92 chalasin D blocks the FSS-induced changes in NHE3 and Na/K-ATPase, but not V-ATPase.

93 tools; they also had reduced levels of total NHE3 and NHERF1 compared with control mice.

94 ed well with a change in co-precipitation of NHE3 and NHERF2 but not NHERF1.

95 ound that the expression of Na+/H+ exchanger NHE3 and several scaffold proteins, including NHE3 regul

96 ) increased expression and protein levels of NHE3 and SGLT1 in the brush border membrane.

97 ocked the ANG II-induced binding of IRBIT to NHE3 and the increase in NHE3 surface abundance.

98 Caco-2BBe cells that express NHE3 and the sodium/glucose cotransporter 1 (SGLT1) were

99 employed FRET to study close association of NHE3 and these NHERFs and fluorescence recovery after ph

100 e role of fluid shear stress (FSS) on apical NHE3 and V-ATPase and basolateral Na/K-ATPase traffickin

101 in expression, and a translocation of apical NHE3 and V-ATPase from the intracellular compartment to

102 reabsorption is due to a modulation of both NHE3 and vacuolar H(+)-ATPase (V-ATPase) activity.

103 NKCC2, at Ser552 of the Na(+):H(+) exchanger NHE3, and at Ser552 of beta-catenin.

104 he interaction and colocalization among D3R, NHE3, and USP48; inhibited USP48 activity (-35+/-6%, vs.

105 nd immunoblotting with specific anti-phospho-NHE3 antibodies.

106 Thus, CHP1 interaction with NHE3 apparently establishes the exchanger set point for

107 hibitors of the Na(+)/H(+) exchanger type 3 (NHE3) are described based on a hit from high-throughput

108 ther or both might dynamically interact with NHE3 as part of Ca(2+) signaling.

109 -2 are localized at the BB, where they bind NHE3 as well as the cytoskeleton, we tested whether eith

110 reen identified sodium hydrogen exchanger 3 (NHE3) as required for efficient multiplication of LCMV i

111 c acid of activity and increased mobility of NHE3, as well as necessary for inhibition of NHE3 activi

112 5) There were some differences in NHE3-associating proteins in the two PBM mutations.

113 II transiently increased binding of IRBIT to NHE3 at 5 min but became dissociated by 45 min.

114 ese studies show that phosphorylation of the NHE3 at a single amino acid in the distal part of the C-

115 f NHE3 is associated with phosphorylation of NHE3 at Ser(554), Ser(607), and Ser(663), all of which a

116 exchanger isoform 3 (NHE3), distribution of NHE3 at the base of the microvilli, and less abundant ex

117 The conclusions were: 1) NHE3 basal activity is regulated by a signaling complex

118 ium inhibition of NHE3 activity by anchoring NHE3 basally and releasing it with elevated Ca(2+).

119 minal perfusion with 40 mM glucose inhibited NHE3 because of cell swelling.

120 CaMKIIgamma associates with NHE3 between aa 586 and 605 in the NHE3 C terminus in a

121 mplex formation, because when it is mutated, NHE3 binding to PLC-gamma as well as NHERF2 is lost.

122 reduced basal NHE3 activity as well as ezrin-NHE3 binding, and this effect was eliminated in NHE3-S52

123 dies demonstrate that CaMKIIgamma is a novel NHE3-binding protein, and this association is reduced by

124 In conclusion, NHE3 binds to NHERF proteins via both an internal Class

125 e and cooperative for dopamine inhibition of NHE3 but reversed that of adenosine.

126 CaMKII inhibits NHE3 by an effect on its turnover number, not changing s

127 itically involved in mediating activation of NHE3 by ANG II via a Ca(2+)/calmodulin-dependent protein

128 The stimulation of NHE3 by ANG II was dependent on changes in [Ca(2+)](i) a

129 HERF2 and does not support the inhibition of NHE3 by carbachol.

130 HERF2 significantly attenuated regulation of NHE3 by Dex but did not completely obliterate the effect

131 study, we compared short-term regulation of NHE3 by Dex in SGK1-null and NHERF2-null mice.

132 Activation of SGK3 and NHE3 by Dex was dependent on phosphoinositide 3-kinase (

133 PS120 cells resulted in robust activation of NHE3 by Dex.

134 factor 2 (NHERF2) and mediates activation of NHE3 by dexamethasone (Dex) in cultured epithelial cells

135 activity associated with phosphorylation of NHE3 by effects requiring aa downstream of NHE3 aa 690 a

136 udy tested the hypothesis that cGMP inhibits NHE3 by phosphorylating it and altering its membrane tra

137 2) Dexamethasone stimulates NHE3 by phosphorylation of a single site, Ser(663).

138 internal region (amino acids 586-660) of the NHE3 C terminus and to the NHE3 C-terminal four amino ac

139 CaMKII binding to and phosphorylation of the NHE3 C terminus are parts of the physiologic regulation

140 In vitro, NHERF3 bound the NHE3 C terminus between amino acids 588 and 667.

141 1) The F1 domain of the NHE3 C terminus has phosphoinositide binding regions.

142 ates with NHE3 between aa 586 and 605 in the NHE3 C terminus in a Ca(2+)-dependent manner, with less

143 Recombinant AKT phosphorylated NHE3 C terminus in the domain ezrin directly binds.

144 SK-3, which act on a Ser cluster in the same NHE3 C-terminal domain that binds ezrin; and 2) these ki

145 s 586-660) of the NHE3 C terminus and to the NHE3 C-terminal four amino acids.

146 His(6) proteins were made from the NHE3 C-terminal region divided into four parts as follow

147 Casein kinase 2 (CK2) binds to the NHE3 C-terminus and constitutively phosphorylates a down

148 e we show that SNX27 directly interacts with NHE3 (C-terminus) primarily through the SNX27 PDZ domain

149 sts and polarized Caco-2BBe cells expressing NHE3, CaMKII inhibits basal NHE3 activity, because the C

150 Apical exocytosis of NHE3, CFTR (cystic fibrosis transmembrane conductance re

151 1) Under basal conditions, NHE3 closely associates with NHERF2 in opossum kidney ce

152 Surprisingly, rat NHE3 co-immunoprecipitated Nedd4-2, but its expression a

153 Similarly, in Caco-2BBe cells, NHERF3 and NHE3 colocalized in the BB under basal conditions but af

154 , immunofluorescence experiments showed that NHE3 colocalizes with SGLT2 but not SGLT1 in the rat ren

155 f the C-terminus affects multiple aspects of NHE3 complex formation and changes the NHE3 lipid raft d

156 The S719A mutant had reduced NHE3 complex size, reduced expression in lipid rafts, in

157 CHP1 may serve as a regulatory cofactor for NHE3 conformational change, dependent on intracellular p

158 Activation of NHE3 corrects cholera toxin-induced defects in Na absorp

159 3) The magnitude of serum stimulation of NHE3 correlates with PI(4,5)P(2) and PI(3,4,5)P(3) bindi

160 Loss of mTOR regulation of NHE3 could mediate the development of diarrhea in patien

161 Second, NHE3-dependent absorption of HCO(3)(-), measured by sing

162 itions, LPA increased fluid absorption in an NHE3-dependent manner and restored the net fluid loss in

163 of ClC-5, whereas the total protein level of NHE3 did not change.

164 NHE3 directly binds Na(+)/H(+) exchanger regulatory fact

165 NHE3 distribution was assessed by cell-surface biotinyla

166 orylation of Na(+)/H(+) exchanger isoform 3 (NHE3), distribution of NHE3 at the base of the microvill

167 by Phlorizin produced a marked inhibition of NHE3, even in the absence of glucose.

168 Under basal conditions, NHERF2 and NHE3 exhibited robust FRET signaling.

169 Na(+)/H(+) exchanger NHE3 expressed in the intestine and kidney plays a major

170 g/min, 4 d) in C57Bl/6J mice increased renal NHE3 expression (+310+/-15%, vs. vehicle), whereas an in

171 uitinylated NHE3 (+140+/-10%); and decreased NHE3 expression (-50+/-9%) in human renal proximal tubul

172 n between D3R and USP48 in the regulation of NHE3 expression and function.

173 onstituted these macrocomplexes and restored NHE3 expression in the BBM.

174 blot analyses indicate that neither NHE2 nor NHE3 expression is altered in apical membranes of inflam

175 d to identify whether NHE isoforms (NHE2 and NHE3) expression is altered and how Na(+) absorption is

176 2) and Arg(520)-Arg(552)) are present in the NHE3 F1 domain; both regions are important for serum sti

177 4,5)P(2) and PI(3,4,5)P(3) bound only to the NHE3 F1 fusion protein (amino acids 475-589) on liposoma

178 quirement for three phosphorylation sites in NHE3 for cGKII inhibition, and for phosphorylation of on

179 min of A23187 (0.5 mum) exposure, the NHERF2-NHE3 FRET signal was abolished, and BB NHE3 mobility was

180 t1/2=21.8 h), indicating that USP48 protects NHE3 from degradation via deubiquitinylation.

181 ired for the exocytosis (not endocytosis) of NHE3 from early endosome to plasma membrane.

182 pendent; was associated with dissociation of NHE3 from NHERF2 and an increase in the NHE3 mobile frac

183 ) abrogated the inhibitory effect of cAMP on NHE3 function via an IP(3) receptor-dependent mechanism.

184 d intracellular Ca(2+), we hypothesized that NHE3 had to be, at least transiently, released from the

185 ), whereas overexpression of USP48 increased NHE3 half-life (t1/2=21.8 h), indicating that USP48 prot

186 internal PBM mutation but no change in total NHE3 half-life in either.

187 However, there is a paradox in that NHE3 has limited mobility in the BB due to its binding t

188 We found that Nedd4-2 ubiquitinated human NHE3 (hNHE3) and altered its expression and activity.

189 ovel endosomal kinase that acutely regulates NHE3 in a PI3K-dependent mechanism.

190 r, these findings indicate the importance of NHE3 in diabetic diarrhea and suggest LPA administration

191 of low doses of rapamycin reduced levels of NHE3 in intestinal tissues; this effect was not observed

192 ant reduction in half-life of the PM pool of NHE3 in only the internal PBM mutation but no change in

193 asal NHE3 activity and surface expression of NHE3 in polarized epithelial cells.

194 ssociated with reduced surface expression of NHE3 in proximal tubules.

195 e analysis showed that SGK3 colocalized with NHE3 in recycling endosomes, whereas SGK1 and SGK2 were

196 and consequent regulation of Na/K-ATPase and NHE3 in renal proximal tubule may contribute to salt-ind

197 nd induced redistribution of Na/K-ATPase and NHE3 in renal proximal tubules.

198 BIT) plays a critical role in stimulation of NHE3 in response to elevated intracellular Ca(2+) concen

199 naling and redistribution of Na/K-ATPase and NHE3 in the Dahl R rats, but not in the Dahl S rats.

200 ads to activation of Na(+)-H(+) exchanger 3 (NHE3) in the intestine by a process that is not dependen

201 rmation about the function and regulation of NHE3 (including its role in regulating paracellular Ca2+

202 Indeed, CHP1 interaction with NHE3 inhibited NHE3 transport in a pHi -dependent manner

203 ture of 13d then provided 3D-QSAR models for NHE3 inhibition capturing guidelines for optimization.

204 ent Na(+) absorption are inhibited by S3226 (NHE3-inhibitor), but not by HOE694 (NHE2-inhibitor) in n

205 f potent, selective, and orally bioavailable NHE3 inhibitors with 13d as best compound, showing high

206 y, Phlorizin-sensitive SGLT transporters and NHE3 interact functionally in the proximal tubule.

207 o multiple proteins that bind throughout the NHE3 intracellular C-terminus, including calcineurin hom

208 epithelial brush-border Na(+)/H(+) exchanger NHE3 is acutely inhibited by cGKII/cGMP, but how cGKII i

209 We conclude that 1) cGMP inhibition of NHE3 is associated with phosphorylation of NHE3 at Ser(5

210 d surface protein abundance, confirming that NHE3 is downstream of ezrin.

211 ntly expressed in the proximal tubules where NHE3 is located.

212 This overall phosphorylation of NHE3 is not affected by the presence of NHERF2.

213 Back phosphorylation demonstrated that NHE3 is phosphorylated by CaMKII under basal conditions.

214 The brush border (BB) Na(+)/H(+) exchanger NHE3 is rapidly activated or inhibited by changes in tra

215 ibited by cGKII/cGMP, but how cGKII inhibits NHE3 is unknown.

216 The Na(+)/H(+)-exchanger 3 (NHE3) is essential for regulation of Na(+) transport in

217 Na(+)/H(+) exchanger 3 (NHE3) is the major Na(+) transporter in the intestine.

218 these sites for dexamethasone stimulation of NHE3, is a unique example of regulation by phosphorylati

219 vasculature (NHE1 isoform) and the kidneys (NHE3 isoform) may serve as a common mechanism that links

220 binding phosphoprotein of 50 kDa (EBP50) and NHE3 kinase A regulatory protein (E3KARP) both consist o

221 ts of NHE3 complex formation and changes the NHE3 lipid raft distribution, which cause changes in spe

222 stine is mediated by Na(+)/H(+) exchanger 3 (NHE3), located in the luminal membrane of enterocytes.

223 heterodimerization mediates the formation of NHE3 macrocomplexes, which are required for the inhibiti

224 inin-4, and PKCalpha, promoting formation of NHE3 macrocomplexes.

225 as a cause of CSD and implies primary basal NHE3 malfunction as a predisposition for IBD in a subset

226 minal perfusion with 5 mM glucose stimulates NHE3-mediated bicarbonate reabsorption.

227 Lumen butyrate-Ringer incubation activated NHE3-mediated Na(+) absorption in DSS-induced colitis.

228 ether SGLT-mediated glucose uptake regulates NHE3-mediated NaHCO3 reabsorption in the renal proximal

229 e observations indicate that in normal colon NHE3 mediates both HCO3 (-)-dependent and butyrate-depen

230 NHE3(-/-) mice display alterations in epithelial gene an

231 treated, 6- to 8-week-old wild-type (WT) and NHE3(-/-) mice were used for the experiments.

232 n of NHE3 from NHERF2 and an increase in the NHE3 mobile fraction from the brush border; and was acco

233 The dynamics in FRET signal and NHE3 mobility correlated well with a change in co-precip

234 nce recovery after photobleaching to monitor NHE3 mobility in the apical domain in polarized opossum

235 HERF2-NHE3 FRET signal was abolished, and BB NHE3 mobility was transiently increased.

236 n and/or loss of basal transport function of NHE3 molecules, whereas acute regulation was normal.

237 All mutations were in the NHE3 N-terminal transport domain, and all missense mutat

238 Molecular analysis revealed that NHE3, NHERF1, IRBIT, and ezrin form macrocomplexes, whic

239 3) The change in NHE3-NHERF2 association is accompanied by an increased B

240 of elevated Ca(2+), the close association of NHE3-NHERF2 is abolished but is re-established in approx

241 ased the abundance of total and cell-surface NHE3, NKCC2, NCC, alpha-ENaC and cleaved gamma-ENaC comp

242 s also required to regulate the retention of NHE3 on the plasma membrane.

243 hough the biophysical and molecular basis of NHE3 pHi sensitivity have not been defined.

244 cGMP/cGKII increased NHE3 phosphorylation at three sites (rabbit Ser(554), Se

245 Identification of NHE3 phosphorylation sites was by iTRAQ/LC-MS/MS with Ti

246 3 and fluid absorption in part by increasing NHE3 protein abundance at the brush border membrane of i

247 Total and percent plasma membrane (PM) NHE3 protein expression was reduced in the C-terminal bu

248 Insertion of a PY motif in rabbit NHE3 recapitulated the interaction with Nedd4-2 and enha

249 HERF2 domain was functionally significant in NHE3 regulation, being necessary for stimulation by lyso

250 oteins that are required for many aspects of NHE3 regulation.

251 HE3 and several scaffold proteins, including NHE3 regulatory factors (NHERFs), inositol trisphosphate

252 asal activity of the BB Na(+)/H(+) exchanger NHE3 requires multiprotein complexes that form on its C

253 USP48 silencing decreased NHE3's half-life (USP48 siRNA t1/2=6.1 h vs. vehicle t1/

254 be cells was further examined by mutation of NHE3-S(719) to A (not phosphorylated) or D (phosphomimet

255 NHE3-S515A and -S526D did not bind ezrin; NHE3-S515D had

256 NHE3-S515A and -S526D did not bind ezrin; NHE3-S515D had reduced ezrin binding; NHE3-S526D bound e

257 3 binding, and this effect was eliminated in NHE3-S526A and -S526D mutants.

258 ezrin; NHE3-S515D had reduced ezrin binding; NHE3-S526D bound ezrin normally.

259 NHE3-S719A but not -S719D had multiple changes in NHE3 a

260 A comparison of NHE3 sequences revealed the presence of PY motifs in NHE

261 NHE3-Ser(526) is predicted to be a GSK-3 kinase phosphor

262 NHE3-Ser(663) phosphorylation was not necessary for cAMP

263 The former determines NHE3 stability in the PM, and the latter determines tota

264 binding of IRBIT to NHE3 and the increase in NHE3 surface abundance.

265 RF1 knockdown; was associated with increased NHE3 surface expression in Caco-2 cells, which also was

266 Parathyroid hormone decreased NHE3 surface expression, but the extent of decrease and

267 ng, and the latter but not the former alters NHE3 surface expression.

268 eatment for an increase in NHE3 activity and NHE3 surface expression.

269 s are parts of the physiologic regulation of NHE3 that occurs in fibroblasts as well as in the BB of

270 -methyl-D-Glu (alpha-MD-G) activated jejunal NHE3; this process required Akt and NHERF2.

271 gulate the dynamic association of ezrin with NHE3 to affect basal NHE3 activity.

272 tion of the isoform 3 Na(+)/H(+) antiporter (NHE3) to demonstrate a functional relevance for CO(2)-me

273 Silencing of NHERF1 or IRBIT prevented NHE3 trafficking to the BBM and insulin-dependent NHE3 a

274 expression of wild-type ezrin increased both NHE3 transport activity and surface protein abundance, c

275 I at physiological concentrations stimulates NHE3 transport activity in a model proximal tubule cell

276 of NHE3, which contributes to inhibition of NHE3 transport activity via increased endocytosis.

277 physiologic metabolism of glucose stimulates NHE3 transport activity, whereas, supraphysiologic gluco

278 Indeed, CHP1 interaction with NHE3 inhibited NHE3 transport in a pHi -dependent manner.

279 Epithelial Na(+)/H(+) exchanger-3 (NHE3) transport is fundamental for renal and intestinal

280 d the hypothesis that phosphoinositides bind NHE3 under basal conditions and are necessary for its ac

281 ANG II-induced activation of NHE3 was abrogated by knockdown of IRBIT, whereas overex

282 Surface NHE3 was determined by cell surface biotinylation.

283 y cell surface biotinylation, trafficking of NHE3 was examined in short hairpin RNA (shRNA) plasmid-t

284 h contributed to the altered distribution of NHE3 was examined.

285 The PLC-gamma-binding site in NHE3 was identified (amino acids 586-605) and shown to b

286 3) cGMP- and Ca(2+)-mediated inhibition of NHE3 was impaired in both the internal and the C-termina

287 is effect was eliminated if ezrin binding to NHE3 was inhibited by a point mutant.

288 activity or increase surface expression when NHE3 was mutated to either S663A or S663D.

289 Surface NHE3 was reduced in opossum kidney cells with reduced ex

290 The expression of NHE3 was reduced in the ileal brush border of patients w

291 Ezrin binding to NHE3 was regulated by Akt, being eliminated by Akti.

292 ification to reduce the CHP1 amount bound to NHE3) was permissive and cooperative for dopamine inhibi

293 l and dexamethasone-stimulated exocytosis of NHE3 were attenuated in ClC-5 knockdown cells.

294 Levels of the Na+/H+ exchanger 3 (NHE3) were measured in human ileal biopsy specimens from

295 NHE3, when complexed with the calcineurin homologous pro

296 SLC9A3 encodes Na(+)/H(+) antiporter 3 (NHE3), which is the major intestinal brush-border Na(+)/

297 panied by an increased BB mobile fraction of NHE3, which contributes to inhibition of NHE3 transport

298 cGMP/cGKII rapidly inhibited NHE3, which was associated with reduced surface NHE3.

299 IRBIT facilitated the interaction of NHE3 with NHERF1 via protein kinase D2-dependent phospho

300 unlike SGK1 or SGK2, SGK3 rapidly activated NHE3 within 15 min of Dex treatment in both PS120 and Ca