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GDNF binds GFRA1 and RET. 29 / 29
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"In support of this idea, coimmunoprecipitation assays reveal constitutive binding between N-CAM and GFRα1, which is in significant contrast to the GFRα1-RET interaction that requires GDNF binding (Ta[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
12837237
sparser
"Examples of such associations between GPI-anchored proteins and transmembrane signaling partners in neurons include the transmembrane protein CASPR and the GPI-linked cell adhesion molecule contactin ( xref ) and binding of GDNF to the receptor complex formed by the GPI-anchored receptor GFRα1 and the transmembrane protein c-Ret ( xref , xref )."
18786358
sparser
"Importantly, expression of FAT4 perturbs the assembly of the RET-GFRA1-GDNF complex, reducing RET signaling."
30853441
sparser
"GDNF binding to its receptors RET and GFRα1 induces both ERK/MAPK and PI3K pathway activation."
27480037
reach
"Thus, without formation of the GDNF, RET, and GFRalpha1 complex, aganglionosis is observed, irrespective of whether the mutation is in RET, GDNF or Gfralpha1 [XREF_BIBR, XREF_BIBR - XREF_BIBR]."
23528997
reach
"This finding is in accordance with RET deficient mice in which they displayed increased gliosis in the SN, suggesting the importance of the GDNF, GFRalpha1, and RET complex in the suppression of inflammation."
18822276
sparser
"GDNF binds to the heteromeric GFRα1-Ret receptor complex, and the receptor complex then binds to and phosphorylates SHC."
19914172
sparser
"The binding of GDNF to Ret and GFRα1 leads to Ret phosphorylation (Kjær and Ibáñez, 2003; Sariola and Saarma, 2003), and thereby leads to the activation of several intracellular signaling pathways, including RAS/mitogen-activated protein kinase/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
"Formation of the GDNF 2 –GFRA1 2 –RET 2 heterohexameric complex results in transphosphorylation of RET, thereby activating the receptor tyrosine kinase signaling pathway [ xref – xref ]."
29088765
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
"Most of these conserved residues are charged, which is consistent with homolog-scanning mutagenesis of RET, indicating that charged residues in the first cadherin-like domain of RET are important for [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16765900
sparser
"Upon formation of the RET-GFRα1-GDNF complex with a stoichiometry of 2:2:2 [ xref ] the tyrosine kinases of the RET dimer autophosphorylate and these phosphorylated tyrosine residues serve as a binding platform for a number of adaptor proteins activating intracellular signaling pathways [ xref ]."
28467503
reach
"The potential binding site for such agonists was searched by examining the protein protein interactions on the binding interface between GDNF and GFRalpha1 in the GDNF, GFRalpha1, and RET complex."
30023796
sparser
"Binding of GDNF-GFRα1 complex to RET results in its activation and phosphorylation of key docking tyrosine residues that signal through pathways including PLCγ, PI3K and MAPK to elicit cellular responses."
22729463
sparser
"The effect of GDNF which preferentially binds the Ret-GFRα1 receptor complex is consistent with the fact that Gfra1 is increased after nerve injury xref ."
24840036
sparser
"Despite the high conservation of the proteins between species, previous research has failed to show any interaction between mammalian RET and non-mammalian GFRα1 or GDNF, or vice versa ."
28467503
sparser
"We sought to provide mechanistic insight into how animals without Ret , Gdnf , or Gfra1 form a ureteric bud and rudimentary kidneys 20–50% of the time ( xref ; xref )."
24143282
sparser
"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 )."
21790653
reach
"These results taken together are compatible with the notion that D4 acts by interfering with the formation of a stable, active RET dimer, regardless of whether dimerization is caused by the formation of the RET, GDNF, and GFRalpha1 complex or by the direct interaction of two mutated RET C634Y proteins."
15769183
sparser
"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
"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-Ret complex."
12673386
reach
"Upon formation of the RET, GFRalpha1, and GDNF complex with a stoichiometry of 2:2:2 [XREF_BIBR] the tyrosine kinases of the RET dimer autophosphorylate and these phosphorylated tyrosine residues serve as a binding platform for a number of adaptor proteins activating intracellular signaling pathways [XREF_BIBR]."
28467503
reach
"In addition to alterations in the nigrostriatal dopamine system resulting in motor impairments associated with a partial loss of GFRalpha1, we can not rule out the possible impact the GDNF, GFRalpha1, and RET complex plays on spinal motoneurons."
18822276
sparser
"Binding of GDNF to its receptors GFRα1 and RET, triggers tyrosine kinase signalling, which induces the outgrowth of the UB."
27480037
reach
"Importantly, expression of FAT4 perturbs the assembly of the RET, GFRA1, and GDNF complex, reducing RET signaling."
30853441
sparser
"Anyway, no interaction between RET and GDNF or GFRα1 co-receptor individually was detectable. xref "
30320260
reach
"The GDNF, GFRa1, and RET complex can activate PI3K (phosphoinositide 3-kinase) intercellular signaling mechanisms and lead to downstream activation of Akt, which then influences the survival and proliferation of SSCs [XREF_BIBR]."
27769051
reach
"Taken together, these data point to the importance of the GDNF, GFRalpha1, and RET complex in the survival and function of the DA system, especially as it relates to increased vulnerability of this system with aging, and also suggest that additive effects of genetic alterations and environmental toxins may be part of the pathology observed in humans with parkinsonian disease patterns."
18822276
sparser
"GDNF and its co-receptor GFRα1 can form a complex with RET and that leads to the activation of RET and its downstream signaling pathways [ xref ]."
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