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GDNF binds GFRA1. 283 / 302
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sparser
"The two receptors also interact with low affinity in the absence of ligand, resulting in the formation of a less selective receptor complex capable of interacting with other members of the GDNF ligand[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
11182089
reach
"Thus, proximal events in RET independent GDNF signaling in RN33B and Schwann cells resemble the intracellular pathways activated by p140 NCAM, both in its time course and in the types of molecules inv[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
12837245
reach
"SORLA facilitates internalization of GFRalpha1 and GDNF complexes from the plasma membrane, resulting in lysosomal catabolism of GDNF but cell surface recycling of GFRalpha1."
27832290
sparser
"With a lower affinity, the GDNF–GFRα1 complex can signal via the RET-independent mechanism with the neural cell adhesion molecule (NCAM); GDNF can also signal independently from GFRα1 by interacting with the heparin sulfate proteoglycan syndecan-3 [ xref , xref ]."
33374485
sparser
"For UB outgrowth, MM cells secrete GDNF which binds to the RET tyrosine kinase receptor and co-receptor GFRa1, both expressed in the nephric duct [ xref , xref , xref ]."
30974877
sparser
"GDNF dimers bind preferentially to GFRα1 with high affinity."
31456664
reach
"GDNF is expressed by the mesenchymal tissue surrounding the growing ureteric bud and binds to the tyrosine kinase receptor Ret and its co-receptor Gfra1, a glycosyl-phosphatidyl inositol linked protein."
19179661
reach
"Here, we find that SorLA acts as sorting receptor for the GDNF and GFRalpha1 complex, directing it from the cell surface to endosomes."
23333276
reach
"As shown in XREF_FIG, GFRA1 directly interacts with GDNF and alternatively, it can bind ARTN or NRTN; GFRA2 binds with NRTN; GFRA3 interacts with ARTN; and GFRA4 is the preferential co-receptor for PSPN."
29617307
reach
"GDNF has been shown to display greater affinity for GFRalpha1b than it does for GFRalpha1a and, as a result, GDNF and GFRalpha1 complexes are more likely to lead to RET phosphorylation at lower ligand concentrations."
25689572
reach
"The Glial cell line derived neurotrophic factor (GDNF) which binds to the receptor GFRA1 is known to play an important role in differentiation and the control of neuron survival."
22808075
sparser
"To understand the molecular mechanisms of ligand receptor interactions, we solved the GDNF-GFRa1 complex structure at 2.35 Å resolution, identified amino acid residues involved in this interaction and residues possibly interacting with RET (Parkash, V., et al. J. Biol."
31817636
reach
"As only GFRalpha1 can bind GDNF directly, receptor complex formation is thought to be initiated by GDNF binding to this receptor."
10545102
reach
"Together, these observations demonstrate the existence of a novel transmembrane receptor partner for the GDNF and GFRalpha1 complex and uncover an unexpected interplay between GDNF-GFRalpha1 and HGF-MET signaling in the early diversification of cortical GABAergic interneuron subtypes."
21807944
biogrid
No evidence text available
10829012
sparser
"And while GFRα1 could bind GDNF, it was not expected to signal due to its lack of an intracellular domain."
32737575
hprd
No evidence text available
9482105
sparser
"The structure was used to model the homologous domain 2, the other half of the GDNF-binding fragment, and to construct the first structural model of the GDNF-GFRalpha1 interaction."
15044950
sparser
"The GPI-linked GFRα1 is localized, at least in part, to lipid rafts, and upon GDNF binding to GFRα1, the complex recruits Ret into the rafts, leading to the activation of the receptor and to the association of Ret with the downstream kinase, Src ( xref ; xref )."
19136027
reach
"However, GDNF can also bind GFRalpha2, and neurturin can bind GFRalpha1, albeit with lower affinities."
18708170
sparser
"High affinity binding of GDNF with GFRα1 occurs only in the presence of RET ( Cik et al., 2000 )."
20347960
sparser
"Three other structurally related members were identified from the GDNF family: neurturin, persephin, and artemin, which bind preferentially to GFRα 2-4 respectively, with GFRα1 preferentially binding to GDNF ( xref )."
34093120
reach
"Although the direct interaction of GDNF with the GFRalpha-1 and NCAM co-receptors may not be the only method to activate Fyn, this study does demonstrate that GDNF promotes SC differentiation via a Fyn dependent mechanism, either through GDNF binding with GFRalpha-1 and NCAM or homophilic binding of NCAM."
24731946
sparser
"The Glial cell line-derived neurotrophic factor (GDNF) which binds to the receptor GFRA1 is known to play an important role in differentiation and the control of neuron survival."
22808075
sparser
"These structures explained why an intact calcium-loaded RET ECD is required for GDNF-GFRα1 binding as the GFRα1 D3 loop-helix α4/GFRα1 D2 helix α1 wedge targets the calcium-dependent CLD(2-3) hinge while the GDNF dimer targets the CRD."
33484636
reach
"Recent data from the crystal structure of the GDNF and GFRalpha1 complex, show basic GDNF residues Arg35, Lys37, and Arg39 to be interacting with sucrose octasulfate, a heparin mimic."
21507484
reach
"GFRalpha1 preferentially binds to GDNF and forms a complex with the transmembrane protein RET to initiate essential intracellular signaling cascades through the Ras-MAPK, phosphoinositol 3-kinase, and Jun N-terminal kinase- and PLCgamma dependent pathways [XREF_BIBR]."
27152762
reach
"An alternative model for Ret activation suggests that the GPI linked GDNF and GFRa-1 complex is first released by lipase from the cell surface and then, as a soluble complex, binds to and activates a [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
9425354
reach
"GDNF preferentially binds to GFRalpha1 and NTN to GFRalpha2, although in vitro studies have suggested that each ligand may be able signal through alternative GFR mechanisms at higher concentrations [XREF_BIBR, XREF_BIBR]."
16716234
reach
"This result is in agreement with our previous results indicating that the GDNF and GFRalpha1 complex plays a crucial role in the development of dendritic arbors and establishment of excitatory synaptic contacts."
29478900
sparser
"GDNF preferentially binds to GFRα1 [ xref ]."
17982417
reach
"In cells expressing c-Ret and GPI anchored protein GFRalpha1 (GDNF family receptor alpha1), which is primarily associated with lipid rafts, the binding of GDNF to GFRalpha1 results in a transient recruitment of c-Ret into the compartment."
15596541
sparser
"GDNF binds to GDNF family receptor alpha 1 (GFRa1), and the resulting complex activates the RET receptor tyrosine kinase and subsequent downstream signals."
32245892
reach
"Unfortunately, the atomic binding surfaces of the GFRalpha1 and GDNF complex to RET are still unknown, so these could not be compared."
28467503
reach
"More importantly, it was inhibited by soluble RET-Fc chimeric protein providing support for a direct interaction between a GDNF, GFR, and alpha1 complex and RET.Current evidence suggests that GDNF bin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
10812967
signor
"A receptor complex comprised of trnr1 (gdnfr alpha) and ret was recently identified and found to be capable of mediating both gdnf and ntn signaling"
9182803
sparser
"We hypothesize that the downregulation of GFRA2 might result in preferential binding of GDNF to GFRA1 (its higher affinity receptor) and promote cell survival."
30221321
reach
"Although GDNF primarily interacts with GFRalpha 1, it can also interact with the NTN- preferring GFRalpha 2 receptor, albeit with lower affinity."
20331804
reach
"High affinity binding of GDNF with GFRalpha1 occurs only in the presence of RET (Cik et al., 2000)."
20347960
reach
"Four different GFRalpha receptors (GFRalpha1-4) have been identified (Baloh et al., 1998; Buj-Bello et al., 1997; Enokido et al., 1998; Jing et al., 1996), and it is now established that GFRalpha1 bin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16765900
sparser
"GDNF binding to GFRalpha1 also recruits Ret to the lipid rafts and triggers association with Src, which is required for effective downstream signalling, leading to differentiation and neuronal survival."
11106404
sparser
"As noted above, responsiveness of SGNs to GDNF and GDNF/GFRα1 suggests the presence of endogenous signaling receptors that mediate intracellular signaling after GDNF binding to GFRα1."
23262364
sparser
"It could be due to: (1) a very low level of GFRa1 is expressed in RA mechanoreceptors, which activates RET in cis in the presence of GDNF; or (2) GFRa1 expressed by neighboring DRG neurons binds GDNF and activates RET in RA mechanoreceptors in trans."
25838128
sparser
"Differences in downstream signaling from GDNF interactions with GFRα1 appear to be widespread."
23262364
sparser
"Following these observations, it was discovered that SorLA binds to GFRα1 with very high affinity and that SorLA is capable of binding to GFRα1 and GDNF simultaneously ( xref )."
32767110
reach
"Some trace residues had been proved to be important in ligand-receptor binding, especially in rat GFRalpha1, where alanine scanning mutagenesis confirmed that sites N (152) N (153), R (259), S (316) N (317) S (318) and Q (247) D (248) S (249) were critical for GFRalpha1 binding to GDNF or Ret and thus affected the formation of GDNF, GFRalpha1, and Ret complex."
12673386
reach
"First, GDNF may be bound by GFRalpha1."
20107080
reach
"While both GDNF and NTN bind GFRalpha1 and GFRalpha2, GDNF binds GFRalpha1 with more efficiency, and NTN binds GFRalpha2 preferentially (Klein et al., 1998; Sanicola et al., 1997)."
20887879
sparser
"Disruption of the niche or related signaling leads to stem cell loss. xref , xref The niche aging in the ovary is associated with the decline in ovarian reproductive function. xref – xref CADHERIN-22, a member of the cadherin superfamily, promotes FGSC self-renewal through interaction with the JAK and β-CATENIN. xref Meanwhile, CADHERIN-22 enhances PI3K-AKT3 signaling, thus, upregulating the expression of N-MYC and CYCLIN, and GDNF-GFRA1 activates AKT3 via PI3K or SFK, subsequently promoting self-renewal of FGSCs. xref GSK3 inhibitor BIO promotes proliferation of FGSCs through activation of β-CATENIN and E-CADHERIN, xref indicating an important role of GSK3 signaling in FGSCs proliferation."
36184610
reach
"XREF_BIBR, XREF_BIBR It has been shown that the GDNF and GFRalpha1 complex can activate not only the canonical GDNF receptor Ret, a receptor tyrosine kinase which signals through the sarcoma protein (Src)/rat sarcoma (Ras)/mitogen-activated protein kinase (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt, NF-kappaB (nuclear factor ' kappa-light-chain-enhancer ' of activated B cells), JNK (c-Jun N-terminal kinases) and PLCgamma (phospholipase gamma) pathway, but also with other signaling inducing receptors."
27607574
sparser
"GDNF preferentially binds to GFRalpha-1 which then interacts with the receptor tyrosine kinase RET."
10408842
reach
"The GDNF and GFRalpha1 complex signals through interactions with the " rearranged during transfection " (RET) receptor or via the neural cell adhesion molecule (NCAM) with a lower affinity."
32046031
sparser
"Effects of gestational inflammation on age-related cognitive decline and hippocampal Gdnf-GFRα1 levels in F1 and F2 generations of CD-1 Mice."
37055728
reach
"GDNF binds to GDNF family receptor alpha 1 (GFRa1), and the resulting complex activates the RET receptor tyrosine kinase and subsequent downstream signals."
32245892
sparser
"The nerve-tumour regulatory axis GDNF-GFRA1 promotes tumour dormancy, imatinib resistance and local recurrence of gastrointestinal stromal tumours by achieving autophagic flux."
35288241
reach
"We show that the GDNF and GFRalpha1 complex inhibits the self-renewal capacity of mouse CNP cells induced by fibroblast growth factor 2 (FGF2), promoting neuronal differentiation."
29478900
reach
"Both GDNF and NTN can interact with either GFRalpha-1 or GFRalpha-2 receptors; however, GDNF preferentially binds to the GFRalpha-1 receptors, while NTN preferentially binds to GFRalpha-2 receptors [XREF_BIBR, XREF_BIBR]."
20119638
reach
"As noted above, responsiveness of SGNs to GDNF and GDNF and GFRalpha1 suggests the presence of endogenous signaling receptors that mediate intracellular signaling after GDNF binding to GFRalpha1."
23262364
sparser
"Unlike hRET, however, the extracellular domain of dRET was unable to interact with mammalian GDNF and GFRalpha1."
15978587
sparser
"This procedure allowed us to identify distinct regions of Ret that are physically engaged in the interaction with GDNF and GFRalpha1."
15722196
sparser
"In vitro binding assays indicate that GDNF binds preferentially to GFRα1, NRTN to GFRα2, ARTN to GFRα3, and PSPN to GFRα4 ( xref )."
20064391
reach
"Activation of the GDNF pathway is initiated via the ligation of GDNF to its co-receptor, GDNF family receptor alpha1 (GFRalpha1), which is a glycosylphosphatidylinositol (GPI)-linked membrane associated protein, and the recruitment of Ret to the GFRalpha1 and GDNF complex (XREF_FIG)."
19136027
reach
"Together, these results demonstrated a neurite outgrowth promoting activity of GDNF on hippocampal and cortical neurons that was dependent on NCAM expression and function and on the activity of Fyn ki[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
12837245
reach
"The GFRalpha-1 receptor was first reported in Cell in 1996 [XREF_BIBR], following its isolation, cloning, and characterization from rat retinal cells; a study which also detailed the interaction between GDNF, GFRalpha-1, and the cRET receptor."
29899247
reach
"Conditional ablation of GFRalpha1 in NSCs indicated that GDNF and GFRalpha1 complex is required for proper maturation and integration of adult-born GCs into preexisting hippocampal circuits."
32714932
reach
"Binding of GDNF to its co-receptor, GFRalpha1 leads to the recruitment of the RTK, Ret, to the GFRalpha1 and GDNF complex, and Ret is then activated by autophosphorylation."
21877259
reach
"GDNF binds with high affinity to the GDNF family receptor alpha-1 (GFRalpha-1) which is expressed in different brain areas."
12535958
reach
"Ret (rearranged during transformation) and the 140 kDa isoform of NCAM (neural cell adhesion molecule) have each been identified as receptors that can bind to the GDNF and GFRalpha1 complex and induce subsequent intracellular signaling, primarily via the PI3K and Akt and/or MEK and Erk MAPK pathways."
23262364
reach
"GDNF predominantly binds to GFRalpha1, NRTN to GFRalpha2, ARTN to GFRalpha3, and PSPN to GFRalpha4."
32252363
reach
"Specifically, activation of RET in cis by GFRalpha1 and GDNF complexes induced a dose dependent 10-fold increase in the number of neurite bearing cells compared to only 2- and 3-fold increases induced[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
10774729
sparser
"GDNF–GFRα1 signaling contributes to synapse development and the maturation of hippocampal neurons [ xref ]."
32188096
reach
"Alternatively, unlike cis binding, trans binding of GDNF and GFRalpha -1 to cRET can occur outside of lipid rafts (Paratcha et al., 2001)."
24099728
reach
"In vitro binding assays indicate that GDNF binds preferentially to GFRalpha1, NRTN to GFRalpha2, ARTN to GFRalpha3, and PSPN to GFRalpha4."
20064391
reach
"As negative controls, we used a scrambled sequence of the D4 aptamer (D4Sc in the XREF_FIG) and the recombinant EC-Ret protein lacking of the domains responsible of the functional interaction between Ret and the GFRalpha1 and GDNF complex (EC-Ret 1-387 in XREF_FIG)."
18286198
sparser
"GFRα1 preferentially binds to GDNF and forms a complex with the transmembrane protein RET to initiate essential intracellular signaling cascades through the Ras-MAPK, phosphoinositol 3-kinase, and Jun N-terminal kinase- and PLCγ-dependent pathways [ xref ]."
27152762
sparser
"There are four glycosyl-phosphatidylinositol-linked GFR receptors (GFRα1-4), which are membrane-anchored and bind their ligands with different affinities: GDNF preferentially binds to GFRα1, neurturin to GFRα2, artemin to GFRα3 and persephin to GFRα4 ( xref ; xref )."
18708170
reach
"We investigated the crystal structure of the mammalian GDNF and GFRalpha1 complex to see if the contact surface in the mammalian GDNF and GFRalpha1 complex is conserved in zebrafish and frog."
28467503
reach
"In a cell culture paradigm of N2aGT cells (neuroblastoma cell line), we show that TGF-beta signaling localizes the GDNF ligand binding receptor GFRa1 to the cell surface, which is a known mechanism by which TGF-beta is able to facilitate GDNF signaling."
23921591
sparser
"Binding of GDNF to GFRα1 and then to RET leads to RET dimerization, tyrosine autophosphorylation and activation of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt, mitogen-activated protein kinase (MAPK) and Src pathways [ xref ] (Fig.  xref , middle)."
32700249
reach
"After binding GDNF, GFRalpha1 mediates downstream signal transduction through interactions with signaling partners such as Ret [XREF_BIBR, XREF_BIBR], which is known to affect TH and DA function [XREF_BIBR]."
23321789
reach
"This established a solid basis for further study to find the key amino acid mediating the binding of GDNF and GFRalpha1."
12625827
reach
"Each GFL has a preferred GFRalpha co-receptor, with GDNF preferentially binding to GFRalpha1, NRTN to GFRalpha2, ARTN to GFRalpha3, and PSPN to GFRalpha4, although cross binding can occur."
32767110
sparser
"In this analysis, the D1 domain of GDNF-GFRα1 or GDF15-GFRAL complexes with RET ECD were missing."
33484636
sparser
"Formation of the GDNF-GFRα1 signaling complex leads to the autophosphorylation of Ret and the subsequent activation of downstream signaling cascades, such as the mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase and phospholipase Cγ/protein kinase C pathway ( xref ; xref )."
19302086
reach
"The GDNF and GFRalpha-1 complex then binds to RET, followed by intracellular signaling cascade activation of several pathways, including RAS and extracellular signal regulated kinase (ERK), p38 mitoge[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
28237042
sparser
"Among these pathways, the nerve-tumour regulatory axis GDNF-GFRA1 is activated in GISTs, assists tumour cells in achieving dormancy and protects them from apoptosis under environmental stress by enhancing autophagic flux."
35288241
reach
"The GDNF/GFRalpha1 complex signals through interactions with the "rearranged during transfection" (RET) receptor or via the neural cell adhesion molecule (NCAM) with a lower affinity."
32046031
sparser
"When two molecules of RET are recruited to the lipid raft by the GDNF-GFRα1 dimeric complex, the two cysteine-rich domains of RET are brought into close proximity, thus promoting dimer formation and the activation of tyrosine kinase xref ."
33150251
reach
"Branching morphogenesis begins with the interaction between the metanephric mesenchyme and the ureteric bud, whereby inductive signals from both embryonic derivatives (GDNF is released from the metanephric mesenchyme and binds to its receptors c-RET and GFRalpha1 at the tips of the ureteric bud) initiate the branching process [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."
25774605
reach
"Thus, GDNF, the earliest discovered factor of the family, binds preferentially to GFRalpha-1, neurturin (NTN) to GFRalpha-2, artemin (ART) to GFRalpha-3, and persephin (PSP) to GFRalpha-4 (Jing et al.[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17825269
reach
"Although both ligands interact with both receptors, cells expressing GFRalpha-1 bind GDNF more efficiently than neurturin, while cells expressing GFRalpha-2 bind neurturin preferentially."
9407096
sparser
"These results suggest an interaction of GFRalpha1 and cRET in the absence of GDNF and demonstrate that the high affinity binding can be measured only when cRET is present."
10829012
sparser
"GDNF binds to GDNF family receptor alpha 1 (GFRα1), causing phosphorylation of the tyrosine kinase receptor RE-arranged during transfection (RET)."
35096711
sparser
"Surprisingly little is known about the intracellular signaling pathways utilized by the GDNF-GFRα1 interaction to mediate cellular effect on dopamine neurons in the in vivo context."
21133924
sparser
"Although there are four GFRA family members, GDNF preferentially binds to GFRA1 to elicit activation of its signaling cascade xref ."
32566252
sparser
"Consistent with the existing models for GDNF–GFRA1 binding, D2 was necessary to mediate the GDF15–GFRAL interaction ( xref )."
32310257
sparser
"Each GFL has a cognate GFRα (GFR) co-receptor that associate as GDNF-GFRα1 ( xref ), NRTN-GFRα2 ( xref ), ARTN-GFRα3 ( xref ), PSPN-GFRα4 ( xref ), and GDF15-GFRAL ( xref ; xref ; xref ; xref ) complexes, respectively."
33484636
reach
"Distinct hydrophobic and positively charged residues in this central region were required for binding of GFRalpha1 to GDNF."
11018032
reach
"Taken together, our results indicate that the GDNF and GFRalpha1 complex is essential for proper hippocampal circuit development."
27707798
reach
"There are four glycosyl-phosphatidylinositol-linked GFR receptors (GFRalpha1-4), which are membrane anchored and bind their ligands with different affinities : GDNF preferentially binds to GFRalpha1, neurturin to GFRalpha2, artemin to GFRalpha3 and persephin to GFRalpha4."
18708170
reach
"The GDNF and GFR-alpha 1 complex may sometimes function independently of RET (see above)."
10812967
reach
"GDNF binds to the GDNF family receptor alpha 1 (GFRa1) and then associates with the proto-oncogene tyrosine protein kinase receptor Ret (C-Ret)."
32867847
sparser
"The soluble Gfra1 stably binds to GDNF to act at a distance to promote neuronal survival and neurite outgrowth on RET-expressing neurons/axons [ xref , xref ]."
21547001
reach
"To test for the possibility that reduced pRET may result from impaired GDNF binding, differentiated SH-SY5Y cells with and without prior PDMP exposure were treated with GDNF followed by washing and ap[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25448159
reach
"GDNF can also bind to GFRalpha2, NRTN to GFRalpha1, and ARTN to GFRalpha1 XREF_BIBR, XREF_BIBR."
29245123
sparser
"In mammalian testis, Fsh treatment is reported to stimulate the expression of GDNF from Sertoli cells, which binds GDNF family receptor alpha-1 (Gfra1) in undifferentiated spermatogonia A, enhancing their self-renewal and maintenance [ xref , xref , xref ]."
30901855
sparser
"In vitro studies have shown that GDNF forms a complex with GDNF family receptor alpha 1 (GFRα1) and acts as an axonal guidance signal during regeneration( xref ; xref ; xref ; xref )."
30081039
sparser
"Similar to the classical NTs, ligand-binding specificity for the GFLs exists with GDNF preferentially binding to GFRα1, but can act via GFRα2 with lower affinity."
34170009
sparser
"The GDNF–GFRα1 complex then binds the RET [ xref , xref ] present on neuronal cell bodies and terminals of several different pathways, such as nigro–striatal dopaminergic neurons [ xref , xref ], spinal motor neurons [ xref ], noradrenergic neurons of the locus coeruleus [ xref ], enteric neurons [ xref ], and sensory neurons [ xref ]."
32046031
sparser
"The GDNF–GFRα1 complex can also bind to and induce signaling through the neural adhesion molecule, NCAM [ xref , xref , xref , xref ]."
32046031
sparser
"As only GFRalpha1 can bind GDNF directly, receptor complex formation is thought to be initiated by GDNF binding to this receptor."
10545102
reach
"GDNF can also bind to either GFRalpha-1 or GFRalpha-2, and activate Ret in the presence of either binding receptor."
9407096
sparser
"GDNF’s interaction with GFRα1, promotes the recruitment, dimerization, and autophosphorylation of the Ret receptor ( xref )."
23373701
reach
"As expected, the positive controls (GDNF in GFRalpha1-RET and soluble GFRalpha1 and GDNF complex in GFP-RET expressing cells) increased RET pY by 3.8-fold (P = 0.0042, RM ANOVA with Dunnett 's post hoc test) and 4.9-fold (P = 0.0465, RM ANOVA with Dunnett 's post hoc test) in GFRalpha1-RET and GFP-RET expressing cells, respectively."
30023796
reach
"A direct test for the relative roles of cis and trans activation in vivo will require tissue specific ablations of GFRalpha1.Upon activation in cis, c-Ret is recruited to membrane rafts by a rapid ext[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
11182089
reach
"GDNF can bind to its ligand specific co-receptor, GDNF family receptor alpha-1 (GFRA1), which is a membrane protein that is expressed in most spermatogonial subtypes in mouse testes including As, Apr, and Aal spermatogonia, triggering signaling via the transmembrane receptor tyrosine kinase RET [XREF_BIBR - XREF_BIBR]."
27769051
reach
"XREF_BIBR, XREF_BIBR, XREF_BIBR GDNF dimers bind to GFRalpha1 (GDNF family receptor alpha-1) with a high affinity, and this complex signals through the transmembrane Ret receptor tyrosine kinase."
25675305
sparser
"Thus, GDNF (200 ng/ml) increased luciferase activity in GFRα1/RET-expressing reporter cells by 59 fold; ARTN (200 ng/ml) in GFRα3/RET-expressing reporter cells by 37 fold, and the complex of soluble GFRα1 and GDNF (200 ng/ml) in RET-expressing reporter cells by only seven fold."
32811276
sparser
"One possible mechanism whereby GDNF may interact with GFRα1 to facilitate dopaminergic pre-synaptic development would be as a ligand-induced cell adhesion molecule, as recently described for hippocampal neurons ( xref )."
21133924
sparser
"GDNF primarily associates with GFRα1, whereas neurturin, artemin, and persephin preferentially bind GFRα2, GFRα3, or GFRα4, respectively [ xref ]."
20951316
sparser
"Heparin neither inhibits nor potentiates GDNF-GFRalpha1 interaction, and the extracellular domain of GFRalpha1 does not bind to heparin itself, precluding heparin cross-bridging of cytokine and receptor polypeptides."
17298301
sparser
"GDNF preferentially binds GFRα1, NRTN preferentially binds GFRα2, ARTN binds GFRα3, and PSPN binds GFRα4 ( xref ; xref )."
26611762
sparser
"Botchkareva et al. had postulated that GDNF-GFRA1 signaling within proximal and distal outer root sheath (ORS) and inner root sheath (IRS) cells of HFs may play a direct role in blocking premature catagen entry based on their in situ mRNA expression pattern of Gfra1 and Gdnf xref ."
32566252
reach
"GDNF, NRTN, ARTN, and PSPN specifically bind to GFR-alpha 1, GFR-alpha 2, GFR-alpha 3, and GFR-alpha 4, respectively, form receptor complexes, and signal through the Ret RTK [XREF_BIBR]."
30845150
reach
"Among the four known GFRalpha subunits, GFRalpha1 preferentially binds to GDNF."
20572899
sparser
"The binding specificity is provided by a cell surface-bound GPI-anchored GDNF family receptor α (GFRα): GDNF preferentially binds to GFRα1, NRTN to GFRα2, ARTN to GFRα3, and PSPN to GFRα4 (Airaksinen and Saarma, xref ; Sidorova et al., xref )."
28680400
sparser
"According to the survival and differentiation responses of these stable PC12 cells upon GDNF stimulation and the GDNF-GFRalpha1-Ret interaction assay, residues 152NN153, Arg259, and 316SNS318 in the GFRalpha1 central region were found to be critical for GFRalpha1 binding to GDNF and eliciting downstream signal transduction."
14563851
reach
"Binding of GDNF and GFRalpha1 complex to RET results in its activation and phosphorylation of key docking tyrosine residues that signal through pathways including PLCgamma, PI3K and MAPK to elicit cellular responses."
22729463
sparser
"Four different GFRα receptors (GFRα1-4) have been identified ( Baloh et al., 1998; Buj-Bello et al., 1997; Enokido et al., 1998; Jing et al., 1996 ), and it is now established that GFRα1 binds prefere[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16765900
biogrid
No evidence text available
9407096
reach
"The lack of these regions in a recombinant Ret form results in the failure of both structural and functional binding of Ret to GFRalpha1 and GDNF complex."
15722196
reach
"Normal budding of the UB from the WD is dependent on glial cell line derived neurotrophic factor (GDNF) interacting with its co-receptors Ret and GFRalpha1."
20816800
reach
"GDNF and GFRalpha1 Complex Is Required to Control Cortical Precursor Proliferation in Response to FGF."
29478900
sparser
"Based on assays with both GPI-anchored and soluble receptors, we therefore conclude that D1 contributes to the optimal function of GFRalpha1 by stabilizing the interaction between GFRalpha1 and GDNF."
15610063
sparser
"It also influences receptor tyrosine kinase RET signaling via interaction with GDNF and its primary receptor GFRα1 ( xref )."
28265003
sparser
"Biochemical and cell culture studies suggest that GDNF binds to GFRα1 requiring the transmembrane tyrosine kinase Ret xref to form a functional receptor complex."
31171625
sparser
"The GDNF (glial cell line-derived neurotrophic factor)-binding receptor GFRalpha1 (GDNF family receptor alpha1) is attached to the membrane by a GPI (glycosylphosphatidylinositol) anchor and consists of three cysteine-rich domains."
15610063
sparser
"PD98059 blocked glial cell line-derived neurotrophic factor-induced PC12-GFRalpha1 cells neurite formation in a dose-dependent manner, without significantly altering cell viability."
11377858
sparser
"The results suggested that GDNF binds to GFRα1 and recruits the co-receptor RET in BMMSCs."
33148376
reach
"In GDNF-RET signaling pathway, GDNF first binds to GFRalpha1 and then binds to and activates RET."
28490466
sparser
"This position for the GFRAL D1 domain arises from a more upright position for GFRAL observed than GDNF-GFRα1 complexes ( xref )."
33484636
hprd
No evidence text available
8674117
reach
"Based on all these data it will be important to continue investigating the contribution of GDNF and GFRalpha1 complex in neurodevelopmental disease characterized by cognitive impairments."
29478900
reach
"GDNF binds with high affinity to the GDNF family receptor alpha-1 (GFRalpha-1), which is highly expressed in the midbrain."
11745638
reach
"In contrast, GDNF binds to GFRalpha1 and GFRalpha2, which both interact with the RET tyrosine kinase receptor to activate multiple pro survival, intracellular signaling pathways."
25438961
reach
"Binding of GDNF to GDNFR-a activates phosphorylation of the protein tyrosine kinase RET, even if GDNFR-a is released from the plasma membrane."
9229113
reach
"GDNF binding to its receptors RET and GFRalpha1 induces both ERK and MAPK and PI3K pathway activation."
27480037
reach
"GDNF forms a complex with GFRalpha1 and promotes the survival of neurons [XREF_BIBR]."
25888394
reach
"GDNF signaling is mediated through a two-component system consisting of the so called GDNF receptor-alfa (GFRalpha1) which binds to GDNF."
10803600
sparser
"Indeed, in MDCK cells and several other cell types, GDNF binding to GFRα1 activates Met indirectly via Src family kinases."
12682085
sparser
"We hypothesize that GDNF interacts with its receptor GFRα1, and signals primarily through RET tyrosine kinase second messenger pathways at the human BNB in vitro during recovery following diffuse endo[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
22326552
sparser
"It has been shown that GDNF binds to GFRα1, NRTN to GFRα2, ARTN to GFRα3 and PSPN to GFRα4."
20350599
sparser
"The complex of GDNF and GFRα1, in turn, recruits a transmembrane rearranged during transfection (Ret) receptor and triggers downstream signaling, which controls mitochondrial morphology and complex I activity in dopaminergic neurons ( xref )."
31736859
sparser
"In cells expressing c-Ret and GPI-anchored protein GFRα1 (GDNF family receptor α1), which is primarily associated with lipid rafts, the binding of GDNF to GFRα1 results in a transient recruitment of c-Ret into the compartment."
15596541
sparser
"Previous studies showed that hRET ECD produced in a glycosylation-deficient Chinese hamster ovary (CHO) Lec8 cell line binds to hGDNF-rat GFRα1 (rGFRα1) ligand with a K d of 15 nM ( Kjaer et al., 20[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25242331
sparser
"The D1 domain is missing from previous structures of GDNF-GFRα1 and GDF15-GFRAL, but had been observed for NRTN-GFRα2 alone or bound to hRET ECD ( xref ; xref )."
33484636
reach
"In vitro studies show that there is preferential binding between GDNF and GFRalpha1."
21337366
reach
"Although GDNF responsiveness is abolished in Gfra1 (-/-) neurons, it can be restored upon addition of soluble GFRalpha1, a result that is only compatible with the existence of a previously unknown transmembrane signaling partner for the GDNF and GFRalpha1 complex in GABAergic neurons."
21807944
sparser
"Glu143 is also strictly conserved in all GFLs ( Figure 4 A) and is one of the most important binding determinants for the interactions between GDNF and GFRα1 ( Eketjall et al., 1999 )."
16765900
reach
"Glial cell line Derived Neurotrophic Factor (GDNF) binds the GFRalpha1 receptor, and the GDNF and GFRalpha1 complex binds to and activates the transmembrane RET tyrosine kinase to signal through intracellular Akt and Erk pathways."
32362584
reach
"Binding of GDNF to GFRA1 triggers RET signaling leading to ER phosphorylation and estrogen independent transcriptional activation of ER dependent genes."
30040982
sparser
"Using chemical crosslinking, it has been demonstrated that a specific interaction between GDNF and GFRα1 occurs with a higher affinity than that between GDNF and GFRα2."
20347960
sparser
"GDNF binds to GFRα1, neurturin activates the GFRα2 receptor, and artemin binds to the GFRα3 receptor."
32116521
sparser
"We did not detect any interaction between PSPN and GFRα1 in SPA system, whereas the positive control with radiolabeled GDNF bound strongly to GFRα1 (data not shown)."
20350599
reach
"To activate Ret, GDNF first binds with high affinity to the coreceptor GDNF receptor alpha-1 (GFRalpha1), and then as a complex, GDNF and GFRalpha1 bind and activate Ret."
20392937
reach
"GDNF binds to the receptor complex of Ret and Gfra-1 on NCCs, and Ret expression by NCCs is essential for GDNF induced migration."
15337776
reach
"A precedent for the potential therapeutic effects of neurotrophic factors in injured salivary glands has already been demonstrated in vivo with administration of GDNF or Neurturin, which bind Gfra1 and Gfra2 receptors and improve saliva secretion post-irradiation (Ferreira, et al., 2018; Xiao, et al., 2014; Knox, et al., 2013)."
33305192
sparser
"GDNF preferentially binds to the GFRα1, which then activates the receptor tyrosine kinase RET or the neural cell adhesion molecule ( xref )."
26611762
reach
"The GPI linked GFRalpha1 is localized, at least in part, to lipid rafts, and upon GDNF binding to GFRalpha1, the complex recruits Ret into the rafts, leading to the activation of the receptor and to the association of Ret with the downstream kinase, Src."
19136027
reach
"In conclusion, the SMN by down-regulating GDNF and its receptor gfralpha1 expression inhibits GDNF and gfralpha1 complex generation and consequently suppresses Bcl-6b expression."
30195499
sparser
"The HIRmAb section of the fusion protein binds the BBB HIR to mediate transport to the brain, and the GDNF of the fusion protein binds to GFRalpha1 to mediate GDNF pharmacologic action (15)."
22745701
sparser
"Each GFL has a preferred GFRα co-receptor, with GDNF preferentially binding to GFRα1, NRTN to GFRα2, ARTN to GFRα3, and PSPN to GFRα4, although cross-binding can occur ( xref )."
32767110
sparser
"GDNF binds to GFRα1 and then forms a complex with RET as a signaling component (Table xref )."
30608586
reach
"However, in a RET independent pathway, GPI anchored GFRA1 is localized to lipid rafts in the plasma membrane and then, the GDNF and GFRA1 complex triggers a Src dependent signaling pathway, leading to neuronal differentiation and survival [XREF_BIBR]."
29617307
reach
"According to the survival and differentiation responses of these stable PC12 cells upon GDNF stimulation and the GDNF-GFRalpha1-Ret interaction assay, residues 152NN153, Arg259, and 316SNS318 in the GFRalpha1 central region were found to be critical for GFRalpha1 binding to GDNF and eliciting downstream signal transduction."
14563851
reach
"GDNF binding to GFRalpha1 also recruits Ret to the lipid rafts and triggers association with Src, which is required for effective downstream signalling, leading to differentiation and neuronal survival."
11106404
reach
"Glu143 is also strictly conserved in all GFLs and is one of the most important binding determinants for the interactions between GDNF and GFRalpha1 (Eketjall et al., 1999)."
16765900
reach
"As GFRalpha1 possesses no transmembrane domain, intracellular signalling by the GDNF and GFRalpha1 complex is induced via recruitment of one of two co-receptors : REarranged during Transfection (RET) or intracellular domain containing isoforms of neural cell adhesion molecule (NCAM)."
25689572
reach
"With a lower affinity, the GDNF and GFRalpha1 complex can signal via the RET independent mechanism with the neural cell adhesion molecule (NCAM); GDNF can also signal independently from GFRalpha1 by interacting with the heparin sulfate proteoglycan syndecan-3 [XREF_BIBR, XREF_BIBR]."
33374485
sparser
"The GDNF–GFRα1 complex is essential for proper hippocampal circuit development."
32188096
reach
"The results suggested that GDNF binds to GFRalpha1 and recruits the co-receptor RET in BMMSCs."
33148376
sparser
"This established a solid basis for further study to find the key amino acid mediating the binding of GDNF and GFRalpha1."
12625827
reach
"Although ligand binding for these receptors is somewhat promiscuous, GDNF preferentially binds to GFRalpha-1, and neurturin (a GDNF homologue) binds to GFRalpha-2 [7,18,19]."
11551746
reach
"GDNF binds to GFR-alpha1 thereby activating RET, which leads to the activation of the intracellular tyrosine kinase domain."
26388717
sparser
"In addition to the classical GDNF-GFRα1-Ret pathway, GDNF can bind to adhesion proteins such as E-cadherin and NCAM via GFRα1 in a Ret-independent way."
27394444
reach
"We hypothesize that the downregulation of GFRA2 might result in preferential binding of GDNF to GFRA1 (its higher affinity receptor) and promote cell survival."
30221321
sparser
"In addition, we found that the GDNF-GFRA1 axis protects tumor cells from apoptosis under metabolic stress via regulating lysosomal functions and autophagy flux, and participates in the regulation of cytosolic calcium ion signalling in a RET-independent and non-canonical way."
36808605
reach
"The established signaling mechanism for the GDNF and GFRalpha -1 complex is through binding to the tyrosine kinase receptor encoded by the c-ret proto-oncogene, and we also show here that c-ret mRNA is upregulated in both motoneurons and primary sensory neurons of aged rats."
10398293
sparser
"On the contrary, BSCs do express Gfra2 xref , suggesting the possibility that the GFRA2-neuturin network may also be compromised upon Ret ablation in addition to impairment of the GFRA1-GDNF network."
32566252
reach
"First, GDNF binds to GFRalpha1 in the absence of Ret."
12682085
reach
"The HIRmAb section of the fusion protein binds the BBB HIR to mediate transport to the brain, and the GDNF of the fusion protein binds to GFRalpha1 to mediate GDNF pharmacologic action (15)."
22745701
sparser
"Binding of GDNF to its receptor, GFRα1, recruits a tyrosine kinase, RET, into rafts where it undergoes autophosphorylation, a process that protects it from proteasomal degradation (Pierchala et al., xref )."
29459819
reach
"In vitro binding experiments with soluble forms of RET, RETL1 and RETL2 demonstrate that while RETL1 binds GDNF tightly to form a membrane associated complex which can then interact with RET, RETL2 only forms a high affinity complex with GDNF in the presence of RET."
9177201
sparser
"GDNF first binds to the glycosylphosphatidylinositol (GPI)-anchored co-receptor GDNF family receptor alpha-1 (GFR α 1) and then the GDNF-GFR α 1 complex binds to, and activates the transmembrane receptor tyrosine kinase RET."
32508331
sparser
"The interaction of GFRα1 with GDNF, a signaling molecule with a TGFβ fold, mediates binding and activation of the Ret tyrosine kinase receptor."
10199408
reach
"Binding of GDNF to GFRA1 and RET also triggers the activation of the canonical RAS-ERK1/2 pathway and regulates SSCs proliferation through the activation of another transcription factor, FOS (XREF_FIG)."
21790653
reach
"The heparin binding sequence is quite distinct from the binding site for the high affinity GDNF polypeptide receptor, GFRalpha1 (GDNF family receptor alpha1), and heparin bound GDNF is able to bind GFRalpha1 simultaneously."
17298301
reach
"The soluble Gfra1 stably binds to GDNF to act at a distance to promote neuronal survival and neurite outgrowth on RET expressing neurons and axons [XREF_BIBR, XREF_BIBR]."
21547001
reach
"GDNF binds to GFRalpha1 and then forms a complex with RET as a signaling component."
30608586
reach
"However, the signaling mechanisms of the GDNF and GFRalpha1 complex in SGNs have not been investigated, and it is not known whether the reported survival effects are mediated by NCAM, Ret of both molecules, downstream of the initial binding of GDNF to GFRalpha1."
23262364
reach
"In this case, GPI anchored GFRA1 and soluble GDNF form a complex that induces cell adhesion working in a similar status (XREF_FIG C)."
29617307
reach
"Several of the mutants produced at 30 degrees C regained their ability to bind to the GDNF and GFRalpha1 complex comparable to wild-type, demonstrating that the mutations affected RETECD folding but not function."
12915470
sparser
"From our data we conclude that TAMs, homing around metastatic nests, induce the autophagy flux of GC cells and promote the development of liver metastasis via GDNF-GFRA1 signalling."
36808605
reach
"GDNF and NRTN preferentially bind to GFR-alpha1 and GFR-alpha2, respectively."
28442998
sparser
"Briefly, GDNF binds its receptor GFRA1 on SSCs, followed by a subsequent signaling of a co-receptor RET, a transmembrane receptor tyrosine kinase, within all undifferentiated spermatogonia, which leads to upregulation in Src family kinase (SFK) signaling and activation of genes encoding key transcription factors (e.g., B cell CLL/lymphoma6, member B ( Bcl6b) , brachyury, Id4, ets variant gene 5 ( Etv5 ), and LIM homeobox protein 1 ( Lhx1 )), leading to self-renewal ( xref ) ( xref )."
28115580
sparser
"This is facilitated by each GFL binding to a preferred glycosyl phosphatidylinositol (GPI)–linked GDNF family receptor α (GFRα) co-receptor, e.g., GDNF predominantly binds to GFRα1, NRTN to GFRα2, ARTN to GFRα3, and PSPN to GFRα4."
29245123
reach
"According to the analysis of binding site for the GFRalpha1 and GDNF complex, the key residues for interactions with a small molecule are Arg171 and Arg224 residues of the receptor which is in line with the previously published data."
30023796
reach
"GDNF preferentially binds to GFRalpha1, neurturin to GFRalpha2, artemin to GFRalpha3 and persephin to GFRalpha4."
29045838
sparser
"Glial cell line-derived neurotrophic factor (GDNF) associates with heparan sulfate in a 2- O -sulfation-dependent manner, promoting the binding of this protein to its receptor component GFRα1 (Rickard et al., xref )."
25852466
reach
"However, c-ret, which is thought to mediate a signal evoked by binding of GDNF to GFRalpha-1, was not expressed in the capillaries of the brain cortex in 3-mo-old rats."
10913002
sparser
"GDNF predominantly binds to GFRα1, NRTN to GFRα2, ARTN to GFRα3, and PSPN to GFRα4."
32252363
reach
"Binding of GDNF to GFRalpha-1 and Ret also leads to the activation of the canonical Ras-Erk1/2 pathway and regulates SSC proliferation."
19306349
reach
"Briefly, GDNF binds its receptor GFRA1 on SSCs, followed by a subsequent signaling of a co-receptor RET, a transmembrane receptor tyrosine kinase, within all undifferentiated spermatogonia, which leads to upregulation in Src family kinase (SFK) signaling and activation of genes encoding key transcription factors (e.g., B cell CLL and lymphoma6, member B (Bcl6b), brachyury, Id4, ets variant gene 5 (Etv5), and LIM homeobox protein 1 (Lhx1)), leading to self-renewal (XREF_FIG)."
28115580
sparser
"Biochemical efforts to map the bipartite GDNF-GFRα1 binding site within RET ECD to a minimal-binding domain have implicated the entire RET ECD region."
33484636
reach
"The GDNF and GFRalpha-1 complex is then recognized by the transmembrane receptor tyrosine kinase RET."
10812965
sparser
"Distinct hydrophobic and positively charged residues in this central region were required for binding of GFRalpha1 to GDNF."
11018032
sparser
"In human pancreatic adenocarcinoma (MiaPaCa-2) cells, GDNF binds to its receptor GFRalpha1, activates the RET co-receptor, and promotes mitogen-activated protein kinase (MAPK) signaling to induce cancer cell migration towards nerve in vitro and animal models of PNI [ xref , xref ]."
| PMC
sparser
"GDNF stimulation can recruit Ret to lipid rafts, suggesting that GDNF-GFRα1 signaling potentiates ephrin-A5 reverse signaling by bringing the co-receptor Ret within close proximity to the GPI-anchored ephrin-A5."
33706917
reach
"GFRalpha1, lacking an intracellular domain, was originally assessed as a binding site for GDNF, serving only in the presentation of the GFRalpha1 and GDNF complex to Ret [7,8,11]."
10601639
reach
"Each family member binds a distinct GFRalpha family co-receptor, such that GDNF, NRTN and ARTN bind GFRalpha1, -alpha2, and -alpha3, respectively."
22216140
sparser
"In the kidneys, RET is activated by interaction with the ligand glial cell line-derived neurotrophic factor (GDNF) and coreceptor GFRα1."
24022366
sparser
"Based on this evidence, we aimed to explore whether Gdnf-GFRα1 expression contributes to cognitive decline in the F1 and F2 generations of mouse dams exposed to lipopolysaccharide (LPS) during late gestation, and to evaluate also the potential interference effect of pro-inflammatory cytokines."
37055728
sparser
"A separate study identified several regions within RET CLD1 that are important for ligand-coreceptor binding whereas characterization of human/ Xenopus RET ECD receptor chimeras implicated human RE[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25242331
reach
"However, GDNF and GFRalpha1 complexes cleaved from the stromal cells were shown to elicit functional signaling through RET expressed on hematopoietic and leukemic cells suggesting a signaling pathway [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
22142702
sparser
"While both GDNF and NTN bind GFRα1 and GFRα2, GDNF binds GFRα1 with more efficiency, and NTN binds GFRα2 preferentially ()."
20887879
reach
"Using chemical crosslinking, it has been demonstrated that a specific interaction between GDNF and GFRalpha1 occurs with a higher affinity than that between GDNF and GFRalpha2."
20347960
reach
"In vitro studies have shown that following GDNF binding to GFRalpha1 the resulting complex recruits RET, leading to its activation by dimerization and autophosphorylation at specific cytoplasmic tyrosine residues, thus initiating a number of downstream intracellular pathways [XREF_BIBR]."
26317008
reach
"GDNF preferentially binds GFRalpha1, NRTN preferentially binds GFRalpha2, ARTN binds GFRalpha3, and PSPN binds GFRalpha4."
26611762
sparser
"GFRα1 mainly binds to GDNF, and GFRα2, 3, and 4 bind NTN, ART, and PSP, respectively [ xref ]."
32438692
reach
"Once activated by the complex GDNF and GFRalpha1, Ret isoforms undergo transphosphorylation on several tyrosine residues, activating the Ras and mitogen activated protein kinase (MAPK) and the phosphatidylinositol-3-kinase and AKT, responsible for cell survival or differentiation, and the phospholipase C-gamma (PLCgamma) pathway."
25675305
reach
"In immortalized cells, BT13 had similar efficacy to GFLs in RET, ERK, and AKT phosphorylation assays; however, in integral luciferase assay the effect of BT13 was much more modest compared with GDNF or soluble GDNF and GFRalpha1 complex."
| PMC
reach
"A final possibility might be that V5 and His tags on C-terminal could decrease NRTN bioactivity based on the finding that the C-terminus on GDNF is very close to the receptor binding site according to the crystal structure of GDNF and GFRalpha1 complex [XREF_BIBR]."
29176874
sparser
"It was suggested that the low-affinity GDNF:GFRα1 interaction, identified by xref in RET-deficient cells, is likely to be due to heparan-sulfate binding."
29245123
reach
"GDNF binds with high affinity to GDNF family receptor alpha-1 (GFR alpha-1)."
10986340
sparser
"Different GDNF-family ligands bind to different α-GDNF family receptors (GFRα): GDNF binds to GFRα1, Neurturin (NTN) binds to GFRα2, Artemin (ARTN) to GFRα3 and Persephin (PSPN) to GFRα4 [ xref ]."
29367572
reach
"GDNF preferentially binds to GFRalpha-1 which then interacts with the receptor tyrosine kinase RET."
10408842
reach
"The GDNF homodimer specifically binds to two GFRalpha1 to form a high affinity complex with the recruitment of Ret proteins."
25762899
reach
"Importantly, this HS binding region of GDNF is distinct from the binding site for the high-affinity GDNF receptor GFR-alpha1; thus, GDNF binds both HS and GFR-alpha1 simultaneously 15."
29066725
reach
"Binding of GDNF and neurturin to human GDNF family receptor alpha 1 and 2."
10829012
reach
"It has been shown that GDNF binds to GFRalpha1, NRTN to GFRalpha2, ARTN to GFRalpha3 and PSPN to GFRalpha4."
20350599
sparser
"Our data provide direct evidence of regionally defined patch-like GDNF-positive signal site in which GFRα1-positive spermatogonia possibly interact with GDNF in the basal compartment of the seminiferous tubules."
22174794
reach
"After GDNF and GFRalpha1 binding, Ret can either signal via the PI3K and Akt- or MEK and Erk-pathways depending upon its localization in lipid raft or non lipid raft compartments at the cell membrane, while NCAM is well recognized to signal via the MEK and Erk-pathway after activation of the Src family kinase Fyn."
23262364
reach
"GDNF binding to the GFRA1 and RET receptor complex (GDNF Receptor Alpha-1 and REarranged during Transfection) induces the activation of two signaling pathways involved in the survival and self-renewal of SSCs (XREF_FIG)."
21790653
reach
"In regards to the mechanism of actions of GDNF in neuroprotection, it has been demonstrated that GDNF binds to GFRalpha1 and Ret receptor complex and in turn activates the inositol triphosphate and the mitogen activated protein kinase intracellular cascades [XREF_BIBR]."
21585328
sparser
"GDNF binds to GFRα1 on the SSC membranes to form the GDNF–GFRα1 complex, which binds and activates RET."
31185583
sparser
"The heparin-binding sequence is quite distinct from the binding site for the high affinity GDNF polypeptide receptor, GFRalpha1 (GDNF family receptor alpha1), and heparin-bound GDNF is able to bind GFRalpha1 simultaneously."
17298301
sparser
"GDNF preferably binds to GFRα1, but studies using GFRα1 knockout mice suggest that GDNF can act via GFRα2 with less affinity (Cacalano et al. xref ; Sariola and Saarma xref ; Schuchardt et al. xref ; Jing et al. xref ; Enomoto et al. xref )."
32897420
sparser
"Comparisons of interfaces within ternary RET complexes either between species (human and zebrafish GDNF-GFRα1) or paralogs (Neurturin-GFRα2 and GDF15-GFRAL) reveal considerable variation in contacts at site 1 and nearly identical contacts at site 2."
33484636
sparser
"These studies revealed that exogenous GFRα1 supplied in soluble form to primary MGE cultures derived from mutant mice lacking GFRα1 could rescue the effects of the mutation, a result that is only compatible with the existence of a transmembrane signaling partner for the GDNF-GFRα1 complex in GABAergic neurons."
32737575
reach
"GDNF preferentially binds to the GFRalpha1, which then activates the receptor tyrosine kinase RET or the neural cell adhesion molecule."
26611762
reach
"The binding of Gdnf to Gfralpha1 triggers phosphorylation of SRC-kinase family proteins followed by activation of PI3K and AKT pathway and eventually leads to self-renewal of SSCs via expression of N-myc gene [XREF_BIBR, XREF_BIBR]."
24817900
reach
"Gain- and loss-of-function assays demonstrate that the GDNF and GFRalpha1 complex promotes dendritic growth and postsynaptic differentiation in cultured hippocampal neurons."
27707798
reach
"GDNF signals through binding to GDNF family receptor alpha-1 (GFRalpha-1) followed by GDNF and GFRalpha-1 complex binding to receptor tyrosine kinase (RET) XREF_BIBR - XREF_BIBR."
28484241
sparser
"Among the four known GFRalpha subunits, GFRalpha1 preferentially binds to GDNF."
20572899
reach
"Based on assays with both GPI anchored and soluble receptors, we therefore conclude that D1 contributes to the optimal function of GFRalpha1 by stabilizing the interaction between GFRalpha1 and GDNF."
15610063
reach
"The binding of GDNF to Ret and GFRalpha1 leads to Ret phosphorylation (Kjaer and Ibanez, 2003; Sariola and Saarma, 2003), and thereby leads to the activation of several intracellular signaling pathways, including RAS and mitogen activated protein kinase and extracellular signal regulated kinase pathway and phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway, which in turn promotes neuronal survival and differentiation (Creedon et al., 1997; Uesaka et al., 2013)."
25317167
sparser
"GDNF preferentially binds to GFRα1, NRTN to GFRα2, ARTN to GFRα3, and PSPN to GFRα4 (Airaksinen and Saarma xref ) (Fig.  xref )."
32556722
reach
"In the mouse, binding of GDNF to its receptor complex GFRA1 and RET activates a number of SRC family kinases (SFKs) that become phosphorylated."
21790653
reach
"The GDNF and GFRalpha1 complex promotes the development of hippocampal dendritic arbors and spines via NCAM."
27707798
reach
"We proceeded from two available crystal structures on the GDNF and GFRalpha1 complex downloaded from Protein Data Bank."
30023796
reach
"This is facilitated by each GFL binding to a preferred glycosyl phosphatidylinositol (GPI)-linked GDNF family receptor alpha (GFRalpha) co-receptor, e.g., GDNF predominantly binds to GFRalpha1, NRTN to GFRalpha2, ARTN to GFRalpha3, and PSPN to GFRalpha4."
29245123
reach
"Although there are four GFRA family members, GDNF preferentially binds to GFRA1 to elicit activation of its signaling cascade 24."
32566252
sparser
"Thus, both in the central and peripheral nervous systems, “ectopic” sites of GFRα1 expression are associated with terminals or axons from GDNF-responsive neurons, in line with the notion that GFRα1 mo[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
11182089
sparser
"Glial cell line-Derived Neurotrophic Factor (GDNF) binds the GFRα1 receptor, and the GDNF-GFRα1 complex binds to and activates the transmembrane RET tyrosine kinase to signal through intracellular Akt/Erk pathways."
32362584
reach
"Cells responded in the expected manner to GDNF, NRTN, or soluble GFRalpha1 and GDNF complex which were used as positive controls."
| PMC
sparser
"GDNF preferentially binds to GFRα1, neurturin to GFRα2, artemin to GFRα3 and persephin to GFRα4."
29045838
reach
"GDNF primarily associates with GFRalpha1, whereas neurturin, artemin, and persephin preferentially bind GFRalpha2, GFRalpha3, or GFRalpha4, respectively [XREF_BIBR]."
20951316
sparser
"However, c-ret, which is thought to mediate a signal evoked by binding of GDNF to GFRalpha-1, was not expressed in the capillaries of the brain cortex in 3-mo-old rats."
10913002
reach
"SSCs self-renew under the influence of glial cell line derived neurotrophic factor (GDNF), which is produced by Sertoli cells and binds to the membrane receptor complex GFRA1 and RET."
28286576
sparser
"Binding of GDNF to GFRA1 triggers RET signaling leading to ER phosphorylation and estrogen-independent transcriptional activation of ER-dependent genes."
30040982
sparser
"However, the signaling mechanisms of the GDNF/GFRα1 complex in SGNs have not been investigated, and it is not known whether the reported survival effects are mediated by NCAM, Ret of both molecules, downstream of the initial binding of GDNF to GFRα1."
23262364
sparser
"The GDNF–GFRα1 complex was observed to promote dendritic growth and postsynaptic differentiation in cultured hippocampal neurons through neural cell adhesion (NCAM) signaling [ xref ]."
32188096
reach
"One possible mechanism whereby GDNF may interact with GFRalpha1 to facilitate dopaminergic pre-synaptic development would be as a ligand induced cell adhesion molecule, as recently described for hippocampal neurons."
21133924
reach
"Different GDNF family ligands bind to different alpha-GDNF family receptors (GFRalpha) : GDNF binds to GFRalpha1, Neurturin (NTN) binds to GFRalpha2, Artemin (ARTN) to GFRalpha3 and Persephin (PSPN) to GFRalpha4 [XREF_BIBR]."
29367572
reach
"GDNF 's interaction with GFRalpha1, promotes the recruitment, dimerization, and autophosphorylation of the Ret receptor."
23373701
reach
"Canonically, the GDNF and GFRA1 complex activates RET to potentiate downstream signaling through the mitogen activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K) pathways, promoting the differentiation, proliferation, and survival of neurons."
29796165
reach
"The GDNF homodimer first binds to GFRalpha1 (either a monomer or dimer), which then interacts with the extracellular domain of two RET molecules and induces their homodimerization and tyrosine autophosphorylation."
30608586
reach
"(c) The GDNF and GFRa-1 complex interacts with two Ret subunits, thereby producing a Ret dimer which can become activated by autotransphosphorylation of the tyrosine kinase domains."
9425354
reach
"Analogously, our data indicate that the recruitment of RET to lipid rafts by GPI anchored GFRalpha1 and GDNF complexes facilitates RET interaction with Src family kinases in vivo, since RET mislocaliz[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
10774729
sparser
"GDNF forms a complex with GFRα1 and promotes the survival of neurons [ xref ]."
25888394
sparser
"As shown in xref , GFRA1 directly interacts with GDNF and alternatively, it can bind ARTN or NRTN; GFRA2 binds with NRTN; GFRA3 interacts with ARTN; and GFRA4 is the preferential co-receptor for PSPN."
29617307
reach
"In vitro studies have shown that following GDNF binding to GFRalpha1 the resulting complex recruits Ret, leading to its activation by dimerization and autophosphorylation at specific cytoplasmic tyrosine residues, thus initiating a number of downstream intracellular pathways XREF_BIBR."
19649251
reach
"GDNF and GFRalpha1 Complex Abrogates Self Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation."
29478900