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1 NHERF contains two amino-terminal PDZ (postsynaptic dens
2 NHERF contains two modular PDZ domains that are modular
3 NHERF directs polarized expression of receptors and ion
4 NHERF is an estrogen-responsive gene that encodes an inh
5 NHERF tumorigenic mutations decreased or abolished its i
6 NHERF was shown previously to be capable of enhancing th
7 NHERF-1 (Na(+)-H(+) exchanger regulatory factor 1, also
8 NHERF-1 null animals challenged with a low phosphate die
9 NHERF-1 null mice demonstrate increased urinary excretio
10 NHERF-1 participates in the inflammatory response that i
11 NHERF-1 reduced the diffusion of the beta(2)AR and the P
12 NHERF-1 reduced the rate of ligand-induced internalizati
13 NHERF-1(-/-) cells also do not adapt to alterations in t
14 NHERF-1(-/-) proximal tubule cells demonstrate defective
15 NHERF-2 immunostaining was associated mainly with the pl
16 NHERF-2 promoted migration and invasion of colon cancer
17 NHERFs were shown to interact directly with platelet-der
18 in Na(+)/H(+) exchanger regulatory factor 1 (NHERF) to assemble protein complexes of cystic fibrosis
19 th the Na+/H+ exchanger regulatory factor 1 (NHERF-1) by binding the first of two PDZ (psd95, discs-l
20 to Na(+)/H(+) exchanger regulatory factor 1 (NHERF-1), a PDZ protein that cross-links membrane protei
21 odium-hydrogen exchange regulatory factor 1 (NHERF-1/EBP50) interacts with the C terminus of several
23 dium-hydrogen exchanger regulatory factor-1 (NHERF-1) plays a key role in the regulation of renal pho
24 by the Na+/H+ exchanger regulatory factor-1 (NHERF-1), an adaptor protein containing two tandem PSD-9
25 dium-hydrogen exchanger regulatory factor-1 (NHERF-1)-null mice were resistant to the inhibitory effe
28 three PDZ adaptor proteins, namely NHERF-1, NHERF-2 and PDZK1, are expressed in the apical membrane,
29 The Na+/H+ exchanger regulatory factor 2 (NHERF-2) is a scaffold protein that regulates cellular s
30 nd the Na+/H+ exchanger regulatory factor 2 (NHERF-2), but the biological effects of these interactio
32 he Na(+)/H(+) exchanger regulatory factor-2 (NHERF-2) is an integral component of almost all endothel
35 in-radixin-moesin-binding phosphoprotein-50 (NHERF-1/EBP50) co-immunoprecipitated with the human kapp
37 sphoprotein, but how phosphorylation affects NHERF to assemble macromolecular complexes is unknown.
41 1)R and NHERF-2 associate in cells, allowing NHERF-2-mediated tethering of P2Y(1)R to key downstream
43 en exchanger regulatory factors (NHERF-1 and NHERF-2) are a family of adaptor proteins characterized
50 nously expressing the CRLR-RAMP3 complex and NHERF-1, the CRLR-RAMP complex desensitizes but is unabl
51 f the concentrated distribution of ezrin and NHERF in the apical membrane regions of epithelial cells
52 Here we examine the interaction of Mrp2 and NHERF-1 and its physiological significance in HEK293 cel
54 mutational analysis indicated that RAMP3 and NHERF-1 interact via a PDZ type I domain on NHERF-1.
55 imal tubule cells derived from wild-type and NHERF-1 knockout animals examines the regulation of NHE3
56 ons occurred at the conserved PDZ domains at NHERF NH2-terminus that bound to SYK, or at its COOH-ter
57 d-type (WT) mice, both sham-operated and BDL NHERF-1(-/-) mice have lower levels of activated ERM and
58 ntrations in serum and liver of sham and BDL NHERF-1(-/-) mice were not significantly different from
59 regulator of endothelial homeostasis because NHERF-2-silenced ECs proliferate at a much higher rate e
62 lasin D disrupts apical localization of both NHERF-1 and the PTH1R and inhibits the PTH-mediated incr
63 of the CRLR-RAMP complex was not affected by NHERF-1 when CRLR was co-expressed with RAMP1 or RAMP2.
65 These data indicate that, in normal cells, NHERF proteins recruit PTEN to PDGFR to restrict the act
66 Na+,K+-ATPase in wild-type OK (OK-WT) cells, NHERF-deficient OKH cells, OK-WT transfected with siRNA
68 gen exchanger regulatory factor-1-deficient (NHERF-1(-/-)) mice demonstrate increases in the urinary
69 aggressiveness, indicating that deregulated NHERF signaling may be associated with disease progressi
71 d other activators of PKC and PKA dissociate NHERF-1/Npt2a complexes, as assayed using quantitative c
72 signaling pathway, in which two PDZ domains (NHERF-2 PDZ2-N2P2 and MAGI-3 PDZ6-M3P6) compete for a re
75 o Chinese hamster ovary cells and endogenous NHERF-1/EBP50 in opossum kidney proximal tubule epitheli
76 bitors calyculin A and okadaic acid enhanced NHERF-1 phosphorylation and inhibited its dimerization.
77 to disruption of the formation of ICAM-1/ERM/NHERF-1 complex and reduction of hepatic ERM proteins an
79 s were observed only in cells that expressed NHERF-1, whereas the PTH1R was localized to bundles that
81 the Na(+)/H(+) exchanger regulatory factor (NHERF) as an important molecular component that stabiliz
83 inds Na(+)/H(+) exchanger regulatory factor (NHERF) family scaffolding proteins that are required for
87 the Na(+)/H(+) exchanger regulatory factor (NHERF), a protein shown to potentiate dimerization of th
88 udy, Na(+)/H(+) exchanger regulatory factor (NHERF)-1 loss-of-function and gain-of-function experimen
89 entified Na+/H+ exchanger regulatory factor (NHERF)-2 as a novel binding partner for the cadherin-ass
90 sodium hydrogen exchanger regulatory factor (NHERF-1) lacking the ezrin-binding domain blocks parathy
91 odium-hydrogen exchanger regulatory factors (NHERF-1 and NHERF-2) are a family of adaptor proteins ch
92 of Na(+)/H(+) exchanger regulatory factors (NHERFs) in regulating SR-BI expression, SR-BI-mediated s
93 proteins, including NHE3 regulatory factors (NHERFs), inositol trisphosphate (IP(3)) receptor-binding
94 llular models, indicate a novel function for NHERF-1 and RAMP3 in the internalization of the AM recep
96 le cells indicate a specific requirement for NHERF-1 for cAMP-mediated phosphorylation and inhibition
97 se studies indicate a unique requirement for NHERF-1 in cAMP regulation of NHE3 and in the traffickin
98 ERF-2 in brain is consistent with a role for NHERF-2 in forming complexes between cell surface and cy
99 OKH cells, OK-WT transfected with siRNA for NHERF (NHERF siRNA OK-WT), and OKH cells that were stabl
100 ial affinity of the Na/P(i) transporters for NHERF-1 and PDZK1 proteins could partially explain their
101 Infection of proximal tubule cells from NHERF-1 null mice with adenovirus-green fluorescent prot
102 that the endothelial neoplasms derived from NHERF-2-silenced cells were much larger in volume than t
106 al tubule cells infected with adenovirus-GFP-NHERF-1 containing an S77A mutation showed significantly
107 l tubule cells with wild-type adenovirus-GFP-NHERF-1 increased basal phosphate transport and restored
108 g in cultured cells expressing wild type GFP-NHERF-1 to define the physiological importance of NHERF-
109 ith adenovirus expressing full-length WT GFP-NHERF-1 increased basal phosphate transport and restored
112 y elevation in cGMP, is used to describe how NHERF family proteins are involved in NHE3 complex forma
119 ated gene transfer, expression of NHERF-1 in NHERF-1(-/-) proximal tubule cells restored the inhibito
124 uric acid uptake was significantly lower in NHERF-1(-/-) cells compared with wild-type cells over a
125 ted by the phosphate content of the media in NHERF-1 null cells although low phosphate media up-regul
126 order membrane (BBM) expression of mURAT1 in NHERF-1(-/-) compared with wild-type control kidneys (P
127 uced apical membrane expression of mURAT1 in NHERF-1(-/-) kidneys and demonstrated mislocalization of
130 and C-terminal domains contact each other in NHERF, but such intramolecular domain-domain interaction
131 es of protein interaction modules present in NHERF/EBP50 (Na+/H+ exchanger 3 regulatory factor/ezrin-
133 in opossum kidney cells, dopamine increased NHERF-1 phosphorylation at serine 77 of the PDZ I domain
136 xin/moesin-binding phosphoprotein of 50 kDa (NHERF/EBP50) family proteins and non-PDZ binding to the
139 cells that were transfected with full-length NHERF-1 or NHERF-1 with mutated PDZ 2 but not in OKH cel
140 mGluR5 robustly associated with full-length NHERF-2 in cells, as assessed by co-immunoprecipitation
143 hosphorylation played key role in modulating NHERF-1 association with plasma membrane targets and ide
147 l tubule, three PDZ adaptor proteins, namely NHERF-1, NHERF-2 and PDZK1, are expressed in the apical
148 lls, OK-WT transfected with siRNA for NHERF (NHERF siRNA OK-WT), and OKH cells that were stably trans
149 The NH(2)-terminal PDZ domain (PDZ 1) of NHERF specifically binds to an internal peptide motif lo
150 he phosphorylation of Thr(95) and Ser(77) of NHERF-1 in the hormonal regulation of renal phosphate tr
152 vation of adenylyl cyclase in the absence of NHERF to principally stimulation of phospholipase C when
154 o NHERF regulates the cooperative binding of NHERF to bring two cytoplasmic tails of CFTR into spatia
155 Our results also demonstrate binding of NHERF to RACK1 at the WD5 repeat, which is distinct from
158 his, in turn, results in the dissociation of NHERF-1 from Npt2a and a decrease in phosphate transport
160 analysis of the subcellular distribution of NHERF-2 immunostaining in four brain structures, cerebra
161 ts demonstrate that the C-terminal domain of NHERF functions as an intramolecular switch that regulat
163 n binding activates the second PDZ domain of NHERF to interact with the cytoplasmic tails of CFTR (C-
164 -339 and Ser-340 in the C-terminal domain of NHERF, but a serine 162 of PDZ2 is specifically protecte
166 , we have identified the first PDZ domain of NHERF-1 as an interaction partner for the PDZ-binding mo
168 rylation at serine 77 of the PDZ I domain of NHERF-1, a site previously shown to attenuate binding of
169 cond of two PSD-95/Dlg/ZO-1 (PDZ) domains of NHERF interacts with a PDZ-binding motif at the very car
170 ein-coupled receptors, the overall effect of NHERF is to enhance the fraction of receptors present at
172 F siRNA OK-WT showed decreased expression of NHERF-1 but equivalent expression of ezrin and Na+,K+-AT
173 ovirus-mediated gene transfer, expression of NHERF-1 in NHERF-1(-/-) proximal tubule cells restored t
175 proteins, and the preferential expression of NHERF-2 in astrocytes suggests that this scaffold protei
183 n functional experiments, the interaction of NHERF-2 with mGluR5 in cells was found to prolong mGluR5
184 lotting confirm the specific interactions of NHERF with the full-length CFTR and with ezrin in vivo.
185 of OK cells expressing a much lower level of NHERF-1/EBP50, U50,488H had no effect on Na(+)/H(+) exch
187 alized at the apical/canalicular membrane of NHERF-1(-/-) mouse hepatocytes, although its immunofluor
188 terminal serines abolished the modulation of NHERF-1 dimerization by phosphatase inhibitors and ident
189 expression of a dominant negative mutant of NHERF enhances EGF-induced receptor down-regulation.
192 how that the hyperproliferation phenotype of NHERF-2-silenced EC is because of an accelerated cell cy
194 for the NHERF PDZ domains, the regulation of NHERF by ezrin may be employed as a general mechanism to
196 een made in our understanding of the role of NHERF proteins in regulation of intestinal Na+ absorptio
201 sphorylation-mimicking mutant S339D/S340D of NHERF has increased affinity and stoichiometry when bind
206 of the ezrin/radixin/moesin (ERM) domain on NHERF-1 indicated that NHERF-1 inhibits CRLR/RAMP3 compl
208 were transfected with full-length NHERF-1 or NHERF-1 with mutated PDZ 2 but not in OKH cells that wer
209 cells knocked down for either N-cadherin or NHERF had impaired ability to migrate into the wounded a
211 ceptor, which does not bind either to NSF or NHERF/EBP50 and interacts selectively with a distinct gr
215 est a novel role for the PDZ adapter protein NHERF-1 in coordinating dopamine signals that inhibit re
218 actions with the cytoplasmic sorting protein NHERF-1 (Na(+)/H(+) exchange regulatory factor-1) and N-
219 s with adenovirus-green fluorescence protein-NHERF-1 resulted in significantly higher rates of uric a
220 ce with adenovirus-green fluorescent protein-NHERF-1 restored the ability of dopamine to stimulate cA
221 )/H(+) exchanger regulatory factor proteins (NHERFs) (NHERF1, NHERF2, PDZ domain-containing kidney pr
223 e (GST)-hKOR C-tail interacted with purified NHERF-1/EBP50, whereas GST or GST-C-tails of micro or de
224 signaling, whereas disruption of the P2Y(1)R-NHERF-2 interaction by point mutations attenuates the du
226 nhances recycling of internalized receptors, NHERF stabilizes EGFR at the cell surface and slows the
227 gment within Naked2; residues 1-173 redirect NHERF-1 from the apical cytoplasm to the basolateral mem
229 n with the second PDZ domain of the scaffold NHERF-2 (Na(+)/H(+) exchanger regulatory factor type 2).
236 oesin (ERM) domain on NHERF-1 indicated that NHERF-1 inhibits CRLR/RAMP3 complex internalization by t
239 mmunohistochemical experiments revealed that NHERF-2 and mGluR5 exhibit overlapping patterns of expre
242 striatum, and cerebellar cortex, showed that NHERF-2 was expressed mainly in astrocytic processes but
245 th SYK promoter methylation, suggesting that NHERF and SYK may transduce a common suppressive signal.
249 revealed important associations between the NHERF proteins and several G protein-coupled receptors s
251 lls and the diverse binding partners for the NHERF PDZ domains, the regulation of NHERF by ezrin may
255 To further evaluate the specificity of the NHERF family in calcium regulation of NHE3 activity, the
260 sport involves phosphorylation of S77 of the NHERF-1 PDZ I domain and the dissociation of NHERF-1/Npt
261 Actin is also an integral component of the NHERF-1-assembled complex because cytochalasin D disrupt
264 NHERF1, NHERF2, and NHERF3 belong to the NHERF (Na(+)/H(+) exchanger regulatory factor) family of
268 to study close association of NHE3 and these NHERFs and fluorescence recovery after photobleaching to
269 tions and heterodimerizations of these three NHERF proteins by pulldown and co-immunoprecipitation as
276 that binding of the FERM domain of ezrin to NHERF regulates the cooperative binding of NHERF to brin
277 We hypothesize that binding of the KOR to NHERF-1/EBP50 facilitates oligomerization of NHERF-1/EBP
278 er-based kinase activity reporter for PKD to NHERF scaffolds reveals a unique signature of PKD activa
280 n CFTR-null mice, PLCbeta2 was undetectable, NHERF-1 mislocalized, and IP3 R3 more intensely stained,
282 contrast to beta-adrenergic receptors where NHERF enhances recycling of internalized receptors, NHER
283 teraction of LPA(2) with Galpha(12), whereas NHERF-2 preferentially promoted interaction between LPA(
284 (PDZ)-scaffolding proteins, three of which (NHERFs 1-3) are localized to the brush border in kidney
290 catenin and N-cadherin are in a complex with NHERF and PDGF-Rbeta at membrane ruffles in the highly i
292 tin and PLCbeta1 and -beta3 co-localize with NHERF-1 and the PTH1R in OKH-N1 cell apical patches.
293 death, whereas coexpression of mGluR1a with NHERF-2 had no evident effects on mGluR1a functional act
294 transient association of PKD1 and PKD2 with NHERF-1 in live cells that is triggered by phorbol ester
296 , we found that coexpression of P2Y(1)R with NHERF-2 in glial cells prolongs P2Y(1)R-mediated Ca(2+)
297 eta), and the interaction of PDGF-Rbeta with NHERF leads to enhanced cell spreading and motility.
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