GDNF signaling (Homo sapiens)

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SMAD3S423S425PROTEIN11086, 104MAP2K2PFOXO3MAPK3Y204T202RET22, 29, 6977, 80, 111806210780Residue / Phosphosite EntericneuronalsurvivalGDNF Signaling PathwayLysosomalprocessingof GDNFCell migrationand chemotaxisof HCC1833 andA549 cellsInMN9DcellsDental pulpstem cellmigration89GFRA1sortingto Trans-GolginetworkProliferationof immaturesertoli cellsGDNF Sorting complex Schwann cellmigration andaxonal growthin hippocampaland corticalneuronsPositive feedbackloop of ST3GAL1 &GDNF/GFRA1 pathwayin breast cancersDopaminebiosynthesisMEN2AHepaticstellatecellactivationProliferation ofpermatogonialprogenitor cellsMigration ofneurons tocortical plateActivationof hedgehogpathway andproliferation& tumor growthCalbindin-positive striatalneurondifferentiationDSG2-mediatedadhesion inenterocytesSelf-renewalin female germlinestem CellsLamellipodia& membraneruffles localized41GDNF-RETinteractionIn MN1cellsIn Schwann cellsMigration andInvasion ofPancreaticCarcinomaCellsNeuronalsurvivalLigandSurvival ofthe entericnervoussystempHEndECF-actin cytoskeletal filament relocation tointercellular membranesExcitation ofDopaminergicneurons in midbrain Molecules/reactions studied to be associated also in RET variantsGM1 Gangliosidep66p52p46Protection ofdopaminergic neurons from6-OHDA toxicityPMtoENMigration ofchondrosarcomacellsSRCfamilykinasesSpermatogonialstem cellproliferationMigrationof SOX1+ Enteric GanglionprecursorsA-type K+channelsMetastasis &migration ofHCT116 & SW480 colon cancercells and U251glioblastomacell line 53Spermatogonialstem cell renewalEnhancement of axonal sprouting, synaptic connectivity & GABAergicneurotransmissionin the spinal cordSuppression ofDifferentiationof SpermatogonialStem CellsNeuro-protectionmTORC1Translocationto lipid rafts18Survival ofgranule andsympatheticneuronsProtection ofdopaminergicneuronsMaintainance oflatency/suppressionof HSV-1reactivationIn substantianigra neuronsBranchingmorphogenesisMigrationof cornealepithelialcellsSuppression oftriglyceridesaccumulation in3T3-L1 adipocytesand HepG2 cellsPKCsSphingosineCa2+44CALB1GAB1PPDLIM7EZRY354Y478PCDHGB7PRETY1096Y1015Y106256T675Y905Y981S696Y68787PXNCEBPBPy69PTK2Y576CRKPPLCG1Y783GAB2SHC1Y427GRB2MAPK7GFRA2GDNFGDNFGFRA1GFRA1O-SialGDNFGDNFGFRA1O-Sial92, 9492, 94 Low affinity bindingRETGDNFHigh-affinitybindingNCAM1GDNF101GFRA3GDNF49GDNFLow affinity binding EfnAEphA2727 Motor axon guidance27 Attractive EPhA reverse signaling in lipid rafts MAP3K14NFKBIAP80NFKB2RELAS536BCL2BCL2L211111177, 111111111PTPN1155555, 7, 11, 36, 51...5PRKACA55 Between RET and other proteins and also between other proteins (without information on phosphosite specificity) SRCY419MAPK955, 97MAPK1PT18580Y18718, 80AKT1T308S47318, 62, 80MAPK3Y204T202T20218, 80MAPK8P805, 39, 80, 865, 18, 62, 975Neuronaldifferentiationof PC12 cells55, 65Neuriteoutgrowth &survival ofsympatheticNeuronsPIK3R154, 80DOK1PBCAR1PRASA1545454GRB7P7, 17GRB104077, 6777, 51777777NRASGTP47, 51, 62FOXO1T24S2566767513838, 62, 9338MEN2BRET/PTC1RET/PTC2RAF1P6962FOS9, 62ATF1PCREB1S1336262In MN1& RM33Bcells62FRS2P45, 85MAPK14T180Y1828045, 8011, 45, 8080NCK16, 62, 80, 95MAP3K3ROCK1PDegradation80979797RHOAGTP77, 42, 861, 498117, 69575757577, 67MAP2K5MEF2C10710710779, 10345MAP2K1P62, 86MAPK1T185Y18762, 69ELK1P26, 6969699999KCND25, 65METP252524101101FYNP101DOK6PIKBKB35PCHUKS18077RAC1GTP8686FOXO1T24S2561515FOXO31339FGF239NCS1757575SLC1A32SLC1A22DOK4P52RAP1AGTP525278NeuriteoutgrowthITGA5POU1F170Anti-apoptosis7042, 4848AKT1T308S47318, 62, 8041PTEN419, 102LRIG1202020BRAF737373PLCG2PCALRPRABEP161PHSPB1S82HSPB1S826161168476, 1063, 1219718431109553, 108891055572216168650, 64ITGB3ITGA5ITGB310510542, 105GAD1GAD2SYPSYN1EGR195CREB1S13395PIK3CBPYWHAZP61PCDHA4P19Statbilizationof active RETIn motor neuronCAD, and SuperiorCervical GangliaCells1919RAP1GAP1010SPHK1GAP4358S1PR1PS1PR3Sphingosine-1-PhosphateP58585858585895NFKB2RELAS5364, 43, 77PIP2IP3DAG7979ITPR1ITPR2797979Ca2+Ca2+Ca2+Ca2+79Calciumreleasefrom ER79797979CAMK2APCAMK2BP79APP63IncreasedAmyloid-beta levelsMTORS2448S248163CDH2Y860888888SORL149, 943131GDNFSORL13131RETGFRA149, 94SORL1RETGFRA1SORL131313131Regulation ofGDNF-induced neurotropicactivity byendocytosisof RETPMtoEN/TGNHIF1AVEGFA535353PPARGFASNSREBF1FABP4SREBF1PPARGC1A50, 64ADRB3ADRB150In brownadipocytes50VAV2PSLC6A384Regulationof Dopaminetransportertrafficking84RPTORS86311089ST3GAL1SP1P2424ST3GAL124SP1P24ITGB1106ITGA6ITGA3AKT3PCCNA2CCNB1CCNE1686868MYCBCL6BETV5LHX1AGRN6868TGFBR116, 109SMAD2S46716424242Ezrin-associatedfliopediaformationROCK2P424232, 91ESR1S167S11891TFF1PGRTOP2A91GDNF-dependentDrug resistancein ER+ breastcancer cells91PRKAR2AP6666671GSK3BS9314-3-3s3LYNPYES1PMYCNP555555CXCL88883333CD2APRETK1107K1060CBLC28, 6028, 60Degradation of RET or dissociation of CD2AP/CBLC complex from RET receptor FAT49898Regulation ofGDNF-GFRA1-RETcomplex assemblyDSG28383SPRY29090SH2B246AP2M12323Clathrin-mediatedinternalizationof RET-51isoform complex341243RPS6KB1T41230GFRA1GDNF49, 9431PMtoLY28, 60RET-51not RET9isoform28, 60GDNFGFRA1GDNFSORL149, 9431313146ERK/AKTindependentsignalingpathwayPDPK173PIP3PIP2ITPR36NANOS29696TH6666VEGFA53, 108VEGFA53, 108ECtoCYFMOD108108CYtoNUCYtoNUCYtoNUCYtoNUCYtoNULIF37Sphingosine-1-Phosphate58GFRA1CYtoNUPMtoENVEGFAsignaling53, 108Monosialotetrahexosylganglioside Mesenchymal cell GDNF-GFRA1interactionregulationReceptors Metabolites/ Secondary messengersProteinfamilymembersPROTEINmRNA PROTEIN / mRNA PROTEIN / mRNA Increased expression Decreased expression Dependent on RET-Y905 phosphorylation Dependent on RET-Y687 phosphorylation Dependent on RET-Y1062 phosphorylation Dependent on RET-Y981 phosphorylation Dependent on RET-Y1015 phosphorylation Multiple edge colours were adopted due to large number of crossing edges for better visualization of reactions Protein- protein interactions Enzyme- substrate reactions Phosphorylation Ubiquitination O-sialylationPROTEIN Post-translational modification type/ site and residue, as reportedResidue / ubiquitination site PROTEINO-Sial Leads to through prior unknown / known mechanisms Multiple edge colours were adopted due to large number of crossing edges for better visualization of reactions Dependent on RET-Y905 phosphorylation Dependent on GFRA1 independent of RET Dependent on RET-Y1062 phosphorylation Dependent on RET-Y687 phosphorylation Dependent on GDNF-NCAM1 interaction Leads to through prior unknown / known mechanisms (Multiple coloured edges were adopted to reduce the complexity in following the pathway reactions)PMCYECENTGNLYNUER Extracellular/secreted Plasma membraneLRLRERLR Lipid rafts Cytoplasm Endosomes Trans-golgi network Endoplasmic Reticulum Lysosome Nucleus Inhibition of molecules / reactions Leads to regulation of gene expression (Multiple coloured edges were adopted to reduce the complexity in following the pathway reactions)FIGURE LEGEND


Description

This pathway shows molecules involved in ligand-receptor interactions and GDNF (Glial cell line-derived neurotrophic factor) receptor activated downstream molecular events including molecular association, enzyme catalysis, translocation, and gene regulation. Information about post-translational modification sites and residues is also depicted.

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  39. Hauck SM, Kinkl N, Deeg CA, Swiatek-de Lange M, Schöffmann S, Ueffing M; ''GDNF family ligands trigger indirect neuroprotective signaling in retinal glial cells.''; Mol Cell Biol, 2006 PubMed Europe PMC Scholia
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  47. Alberti L, Borrello MG, Ghizzoni S, Torriti F, Rizzetti MG, Pierotti MA; ''Grb2 binding to the different isoforms of Ret tyrosine kinase.''; Oncogene, 1998 PubMed Europe PMC Scholia
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  50. Mwangi SM, Nezami BG, Obukwelu B, Anitha M, Marri S, Fu P, Epperson MF, Le NA, Shanmugam M, Sitaraman SV, Tseng YH, Anania FA, Srinivasan S; ''Glial cell line-derived neurotrophic factor protects against high-fat diet-induced obesity.''; Am J Physiol Gastrointest Liver Physiol, 2014 PubMed Europe PMC Scholia
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  53. Huang SM, Chen TS, Chiu CM, Chang LK, Liao KF, Tan HM, Yeh WL, Chang GR, Wang MY, Lu DY; ''GDNF increases cell motility in human colon cancer through VEGF-VEGFR1 interaction.''; Endocr Relat Cancer, 2014 PubMed Europe PMC Scholia
  54. Murakami H, Iwashita T, Asai N, Shimono Y, Iwata Y, Kawai K, Takahashi M; ''Enhanced phosphatidylinositol 3-kinase activity and high phosphorylation state of its downstream signalling molecules mediated by ret with the MEN 2B mutation.''; Biochem Biophys Res Commun, 1999 PubMed Europe PMC Scholia
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  56. Bunone G, Uggeri M, Mondellini P, Pierotti MA, Bongarzone I; ''RET receptor expression in thyroid follicular epithelial cell-derived tumors.''; Cancer Res, 2000 PubMed Europe PMC Scholia
  57. Poteryaev D, Titievsky A, Sun YF, Thomas-Crusells J, Lindahl M, Billaud M, Arumäe U, Saarma M; ''GDNF triggers a novel ret-independent Src kinase family-coupled signaling via a GPI-linked GDNF receptor alpha1.''; FEBS Lett, 1999 PubMed Europe PMC Scholia
  58. Murakami M, Ito H, Hagiwara K, Kobayashi M, Hoshikawa A, Takagi A, Kojima T, Tamiya-Koizumi K, Sobue S, Ichihara M, Suzuki M, Banno Y, Nozawa Y, Murate T; ''Sphingosine kinase 1/S1P pathway involvement in the GDNF-induced GAP43 transcription.''; J Cell Biochem, 2011 PubMed Europe PMC Scholia
  59. Kramer ER, Knott L, Su F, Dessaud E, Krull CE, Helmbacher F, Klein R; ''Cooperation between GDNF/Ret and ephrinA/EphA4 signals for motor-axon pathway selection in the limb.''; Neuron, 2006 PubMed Europe PMC Scholia
  60. Tsui CC, Pierchala BA; ''CD2AP and Cbl-3/Cbl-c constitute a critical checkpoint in the regulation of ret signal transduction.''; J Neurosci, 2008 PubMed Europe PMC Scholia
  61. Hong Z, Zhang QY, Liu J, Wang ZQ, Zhang Y, Xiao Q, Lu J, Zhou HY, Chen SD; ''Phosphoproteome study reveals Hsp27 as a novel signaling molecule involved in GDNF-induced neurite outgrowth.''; J Proteome Res, 2009 PubMed Europe PMC Scholia
  62. Trupp M, Scott R, Whittemore SR, Ibáñez CF; ''Ret-dependent and -independent mechanisms of glial cell line-derived neurotrophic factor signaling in neuronal cells.''; J Biol Chem, 1999 PubMed Europe PMC Scholia
  63. Scholz D, Chernyshova Y, Leist M; ''Control of Aβ release from human neurons by differentiation status and RET signaling.''; Neurobiol Aging, 2013 PubMed Europe PMC Scholia
  64. Mwangi SM, Peng S, Nezami BG, Thorn N, Farris AB 3rd, Jain S, Laroui H, Merlin D, Anania F, Srinivasan S; ''Glial cell line-derived neurotrophic factor protects against high-fat diet-induced hepatic steatosis by suppressing hepatic PPAR-γ expression.''; Am J Physiol Gastrointest Liver Physiol, 2016 PubMed Europe PMC Scholia
  65. Coulpier M, Anders J, Ibáñez CF; ''Coordinated activation of autophosphorylation sites in the RET receptor tyrosine kinase: importance of tyrosine 1062 for GDNF mediated neuronal differentiation and survival.''; J Biol Chem, 2002 PubMed Europe PMC Scholia
  66. Xiao H, Hirata Y, Isobe K, Kiuchi K; ''Glial cell line-derived neurotrophic factor up-regulates the expression of tyrosine hydroxylase gene in human neuroblastoma cell lines.''; J Neurochem, 2002 PubMed Europe PMC Scholia
  67. Segouffin-Cariou C, Billaud M; ''Transforming ability of MEN2A-RET requires activation of the phosphatidylinositol 3-kinase/AKT signaling pathway.''; J Biol Chem, 2000 PubMed Europe PMC Scholia
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  69. You L, Ebner S, Kruse FE; ''Glial cell-derived neurotrophic factor (GDNF)-induced migration and signal transduction in corneal epithelial cells.''; Invest Ophthalmol Vis Sci, 2001 PubMed Europe PMC Scholia
  70. Cañibano C, Rodriguez NL, Saez C, Tovar S, Garcia-Lavandeira M, Borrello MG, Vidal A, Costantini F, Japon M, Dieguez C, Alvarez CV; ''The dependence receptor Ret induces apoptosis in somatotrophs through a Pit-1/p53 pathway, preventing tumor growth.''; EMBO J, 2007 PubMed Europe PMC Scholia
  71. Yang Y, Han C; ''GDNF stimulates the proliferation of cultured mouse immature Sertoli cells via its receptor subunit NCAM and ERK1/2 signaling pathway.''; BMC Cell Biol, 2010 PubMed Europe PMC Scholia
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  75. Nakamura TY, Jeromin A, Smith G, Kurushima H, Koga H, Nakabeppu Y, Wakabayashi S, Nabekura J; ''Novel role of neuronal Ca2+ sensor-1 as a survival factor up-regulated in injured neurons.''; J Cell Biol, 2006 PubMed Europe PMC Scholia
  76. Yazlovitskaya EM, Viquez OM, Tu T, De Arcangelis A, Georges-Labouesse E, Sonnenberg A, Pozzi A, Zent R; ''The laminin binding α3 and α6 integrins cooperate to promote epithelial cell adhesion and growth.''; Matrix Biol, 2019 PubMed Europe PMC Scholia
  77. Sun Y, Huang X, Liu M, Cao J, Chen J, Wang H, Niu H, Yu Z, Yu J, Wang T, Yuan H, Xu X, Gao DS; ''A new alternative NF-κB pathway mediated the neuroprotection of GDNF on 6-OHDA-induced DA neurons neurotoxicity.''; Brain Res, 2012 PubMed Europe PMC Scholia
  78. Yoshida S, Yamamoto N, Wada N, Tomokiyo A, Hasegawa D, Hamano S, Mitarai H, Monnouchi S, Yuda A, Maeda H; ''GDNF From Human Periodontal Ligament Cells Treated With Pro-Inflammatory Cytokines Promotes Neurocytic Differentiation of PC12 Cells.''; J Cell Biochem, 2017 PubMed Europe PMC Scholia
  79. Lundgren TK, Nakahata K, Fritz N, Rebellato P, Zhang S, Uhlén P; ''RET PLCγ phosphotyrosine binding domain regulates Ca2+ signaling and neocortical neuronal migration.''; PLoS One, 2012 PubMed Europe PMC Scholia
  80. Hayashi H, Ichihara M, Iwashita T, Murakami H, Shimono Y, Kawai K, Kurokawa K, Murakumo Y, Imai T, Funahashi H, Nakao A, Takahashi M; ''Characterization of intracellular signals via tyrosine 1062 in RET activated by glial cell line-derived neurotrophic factor.''; Oncogene, 2000 PubMed Europe PMC Scholia
  81. Newburn EN, Duchemin AM, Neff NH, Hadjiconstantinou M; ''GM1 ganglioside enhances Ret signaling in striatum.''; J Neurochem, 2014 PubMed Europe PMC Scholia
  82. Cacalano G, Fariñas I, Wang LC, Hagler K, Forgie A, Moore M, Armanini M, Phillips H, Ryan AM, Reichardt LF, Hynes M, Davies A, Rosenthal A; ''GFRalpha1 is an essential receptor component for GDNF in the developing nervous system and kidney.''; Neuron, 1998 PubMed Europe PMC Scholia
  83. Meir M, Burkard N, Ungewiß H, Diefenbacher M, Flemming S, Kannapin F, Germer CT, Schweinlin M, Metzger M, Waschke J, Schlegel N; ''Neurotrophic factor GDNF regulates intestinal barrier function in inflammatory bowel disease.''; J Clin Invest, 2019 PubMed Europe PMC Scholia
  84. Zhu S, Zhao C, Wu Y, Yang Q, Shao A, Wang T, Wu J, Yin Y, Li Y, Hou J, Zhang X, Zhou G, Gu X, Wang X, Bustelo XR, Zhou J; ''Identification of a Vav2-dependent mechanism for GDNF/Ret control of mesolimbic DAT trafficking.''; Nat Neurosci, 2015 PubMed Europe PMC Scholia
  85. Rizzo C, Califano D, Colucci-D'Amato GL, De Vita G, D'Alessio A, Dathan NA, Fusco A, Monaco C, Santelli G, Vecchio G, Santoro M, de Franciscis V; ''Ligand stimulation of a Ret chimeric receptor carrying the activatingmutation responsible for the multiple endocrine neoplasia type 2B.''; J Biol Chem, 1996 PubMed Europe PMC Scholia
  86. Veit C, Genze F, Menke A, Hoeffert S, Gress TM, Gierschik P, Giehl K; ''Activation of phosphatidylinositol 3-kinase and extracellular signal-regulated kinase is required for glial cell line-derived neurotrophic factor-induced migration and invasion of pancreatic carcinoma cells.''; Cancer Res, 2004 PubMed Europe PMC Scholia
  87. Li XZ, Yan J, Huang SH, Zhao L, Wang J, Chen ZY; ''Identification of a key motif that determines the differential surface levels of RET and TrkB tyrosine kinase receptors and controls depolarization enhanced RET surface insertion.''; J Biol Chem, 2012 PubMed Europe PMC Scholia
  88. Zuo T, Qin JY, Chen J, Shi Z, Liu M, Gao X, Gao D; ''Involvement of N-cadherin in the protective effect of glial cell line-derived neurotrophic factor on dopaminergic neuron damage.''; Int J Mol Med, 2013 PubMed Europe PMC Scholia
  89. Xiao N, Yu WY, Liu D; ''Glial cell-derived neurotrophic factor promotes dental pulp stem cell migration.''; J Tissue Eng Regen Med, 2018 PubMed Europe PMC Scholia
  90. Miyamoto R, Jijiwa M, Asai M, Kawai K, Ishida-Takagishi M, Mii S, Asai N, Enomoto A, Murakumo Y, Yoshimura A, Takahashi M; ''Loss of Sprouty2 partially rescues renal hypoplasia and stomach hypoganglionosis but not intestinal aganglionosis in Ret Y1062F mutant mice.''; Dev Biol, 2011 PubMed Europe PMC Scholia
  91. Morandi A, Martin LA, Gao Q, Pancholi S, Mackay A, Robertson D, Zvelebil M, Dowsett M, Plaza-Menacho I, Isacke CM; ''GDNF-RET signaling in ER-positive breast cancers is a key determinant of response and resistance to aromatase inhibitors.''; Cancer Res, 2013 PubMed Europe PMC Scholia
  92. Treanor JJ, Goodman L, de Sauvage F, Stone DM, Poulsen KT, Beck CD, Gray C, Armanini MP, Pollock RA, Hefti F, Phillips HS, Goddard A, Moore MW, Buj-Bello A, Davies AM, Asai N, Takahashi M, Vandlen R, Henderson CE, Rosenthal A; ''Characterization of a multicomponent receptor for GDNF.''; Nature, 1996 PubMed Europe PMC Scholia
  93. Lee RH, Wong WL, Chan CH, Chan SY; ''Differential effects of glial cell line-derived neurotrophic factor and neurturin in RET/GFRalpha1-expressing cells.''; J Neurosci Res, 2006 PubMed Europe PMC Scholia
  94. Jing S, Wen D, Yu Y, Holst PL, Luo Y, Fang M, Tamir R, Antonio L, Hu Z, Cupples R, Louis JC, Hu S, Altrock BW, Fox GM; ''GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF.''; Cell, 1996 PubMed Europe PMC Scholia
  95. Koelsch A, Feng Y, Fink DJ, Mata M; ''Transgene-mediated GDNF expression enhances synaptic connectivity and GABA transmission to improve functional outcome after spinal cord contusion.''; J Neurochem, 2010 PubMed Europe PMC Scholia
  96. Sada A, Hasegawa K, Pin PH, Saga Y; ''NANOS2 acts downstream of glial cell line-derived neurotrophic factor signaling to suppress differentiation of spermatogonial stem cells.''; Stem Cells, 2012 PubMed Europe PMC Scholia
  97. Encinas M, Tansey MG, Tsui-Pierchala BA, Comella JX, Milbrandt J, Johnson EM Jr; ''c-Src is required for glial cell line-derived neurotrophic factor (GDNF) family ligand-mediated neuronal survival via a phosphatidylinositol-3 kinase (PI-3K)-dependent pathway.''; J Neurosci, 2001 PubMed Europe PMC Scholia
  98. Zhang H, Bagherie-Lachidan M, Badouel C, Enderle L, Peidis P, Bremner R, Kuure S, Jain S, McNeill H; ''FAT4 Fine-Tunes Kidney Development by Regulating RET Signaling.''; Dev Cell, 2019 PubMed Europe PMC Scholia
  99. Yang F, Feng L, Zheng F, Johnson SW, Du J, Shen L, Wu CP, Lu B; ''GDNF acutely modulates excitability and A-type K(+) channels in midbrain dopaminergic neurons.''; Nat Neurosci, 2001 PubMed Europe PMC Scholia
  100. Asai N, Murakami H, Iwashita T, Takahashi M; ''A mutation at tyrosine 1062 in MEN2A-Ret and MEN2B-Ret impairs their transforming activity and association with shc adaptor proteins.''; J Biol Chem, 1996 PubMed Europe PMC Scholia
  101. Paratcha G, Ledda F, Ibáñez CF; ''The neural cell adhesion molecule NCAM is an alternative signaling receptor for GDNF family ligands.''; Cell, 2003 PubMed Europe PMC Scholia
  102. Takashima S, Kanatsu-Shinohara M, Tanaka T, Morimoto H, Inoue K, Ogonuki N, Jijiwa M, Takahashi M, Ogura A, Shinohara T; ''Functional differences between GDNF-dependent and FGF2-dependent mouse spermatogonial stem cell self-renewal.''; Stem Cell Reports, 2015 PubMed Europe PMC Scholia
  103. Borrello MG, Alberti L, Arighi E, Bongarzone I, Battistini C, Bardelli A, Pasini B, Piutti C, Rizzetti MG, Mondellini P, Radice MT, Pierotti MA; ''The full oncogenic activity of Ret/ptc2 depends on tyrosine 539, a dockingsite for phospholipase Cgamma.''; Mol Cell Biol, 1996 PubMed Europe PMC Scholia
  104. Besset V, Scott RP, Ibáñez CF; ''Signaling complexes and protein-protein interactions involved in the activation of the Ras and phosphatidylinositol 3-kinase pathways by the c-Ret receptor tyrosine kinase.''; J Biol Chem, 2000 PubMed Europe PMC Scholia
  105. Su CM, Lu DY, Hsu CJ, Chen HT, Huang CY, Yang WH, Su YC, Yang SN, Fong YC, Tseng WP, Tang CH; ''Glial cell-derived neurotrophic factor increases migration of human chondrosarcoma cells via ERK and NF-kappaB pathways.''; J Cell Physiol, 2009 PubMed Europe PMC Scholia
  106. Zhang X, Mernaugh G, Yang DH, Gewin L, Srichai MB, Harris RC, Iturregui JM, Nelson RD, Kohan DE, Abrahamson D, Fässler R, Yurchenco P, Pozzi A, Zent R; ''beta1 integrin is necessary for ureteric bud branching morphogenesis and maintenance of collecting duct structural integrity.''; Development, 2009 PubMed Europe PMC Scholia
  107. Hayashi Y, Iwashita T, Murakamai H, Kato Y, Kawai K, Kurokawa K, Tohnai I, Ueda M, Takahashi M; ''Activation of BMK1 via tyrosine 1062 in RET by GDNF and MEN2A mutation.''; Biochem Biophys Res Commun, 2001 PubMed Europe PMC Scholia
  108. Chen M, Ba H, Lu C, Dai J, Sun J; ''Glial Cell Line-Derived Neurotrophic Factor (GDNF) Promotes Angiogenesis through the Demethylation of the Fibromodulin (FMOD) Promoter in Glioblastoma.''; Med Sci Monit, 2018 PubMed Europe PMC Scholia
  109. Zajzon K, Pröls F, Heermann S; ''Concerted interaction of TGF-β and GDNF mediates neuronal differentiation.''; Neuroreport, 2013 PubMed Europe PMC Scholia
  110. Wang M, Guo Y, Zhou T, Xue Y, Du G, Wei X, Wang J, Qi L, Zhang H, Li L, Ye L, Guo X, Wu X; ''The Glial Cell-Derived Neurotrophic Factor (GDNF)-responsive Phosphoprotein Landscape Identifies Raptor Phosphorylation Required for Spermatogonial Progenitor Cell Proliferation.''; Mol Cell Proteomics, 2017 PubMed Europe PMC Scholia
  111. Cao JP, Niu HY, Wang HJ, Huang XG, Gao DS; ''NF-κB p65/p52 plays a role in GDNF up-regulating Bcl-2 and Bcl-w expression in 6-OHDA-induced apoptosis of MN9D cell.''; Int J Neurosci, 2013 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
124544view04:24, 8 November 2022EweitzModified description
124543view04:21, 8 November 2022EweitzModified description
120629view19:21, 21 December 2021EgonwUpdated data sources
120553view23:22, 14 December 2021EweitzOntology Term : 'signaling pathway' added !
120552view23:21, 14 December 2021EweitzModified title
120238view01:19, 20 November 2021KeshavNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADRB1Rna153 (RefSeq)
ADRB3Rna115 (RefSeq)
AGRNProteinNP_001292204.1 (RefSeq)
AKT1ProteinNP_005154.2 (RefSeq)
AKT3ProteinNP_005456.1 (RefSeq)
AP2M1ProteinNP_001298127.1 (RefSeq)
APPProteinNP_000475.1 (RefSeq)
ATF1ProteinNP_005162.1 (RefSeq)
BCAR1ProteinNP_001164185.1 (RefSeq)
BCL2L2ProteinNP_001186768.2 (RefSeq)
BCL2ProteinNP_000624.2 (RefSeq)
BCL6BProteinNP_862827.2 (RefSeq)
BRAFProteinNP_004324.2 (RefSeq)
CALB1Rna793 (RefSeq)
CALRProteinNP_004334.1 (RefSeq)
CAMK2AProteinNP_057065.2 (RefSeq)
CAMK2BProteinNP_001211.3 (RefSeq)
CBLCProteinNP_036248.3 (RefSeq)
CCNA2ProteinNP_001228.2 (RefSeq)
CCNB1ProteinNP_114172.1 (RefSeq)
CCNE1ProteinNP_001229.1 (RefSeq)
CD2APProteinNP_036252.1 (RefSeq)
CDH2ProteinNP_001783.2 (RefSeq)
CEBPBProteinNP_005185.2 (RefSeq)
CHUKProteinNP_001269.3 (RefSeq)
CREB1ProteinNP_604391.1 (RefSeq)
CRKProteinNP_058431.2 (RefSeq)
CXCL8Rna3576 (Entrez Gene)
Ca2+Metabolite271 (PubChem-compound)
DAGMetabolite365 (PubChem-substance)
DOK1ProteinNP_001372.1 (RefSeq)
DOK4ProteinNP_060580.2 (RefSeq)
DOK6ProteinNP_689934.2 (RefSeq)
DSG2ProteinNP_001934.2 (RefSeq)
EGR1Rna1958 (RefSeq)
ELK1ProteinNP_001107595.1 (RefSeq)
ESR1ProteinNP_000116.2 (RefSeq)
ETV5ProteinNP_004445.1 (RefSeq)
EZRProteinNP_003370.2 (RefSeq)
EfnAProteinNP_066124.1 (RefSeq)
EphAProteinNP_066124.1 (RefSeq)
FABP4Rna2167 (RefSeq)
FASNRna2194 (RefSeq)
FAT4ProteinNP_001278232.1 (RefSeq)
FGF2Rna2247 (RefSeq)
FMODProtein2331 (Entrez Gene)
FOSRna2353 (RefSeq)
FOXO1ProteinNP_002006.2 (RefSeq)
FOXO3ProteinNP_001446.1 (RefSeq)
FRS2ProteinNP_001265280.1 (RefSeq)
FYNProteinNP_002028.1 (RefSeq)
GAB1ProteinNP_997006.1 (RefSeq)
GAB2ProteinNP_536739.1 (RefSeq)
GAD1ProteinNP_000808.2 (RefSeq)
GAD2ProteinNP_000809.1 (RefSeq)
GAP43Rna2596 (RefSeq)
GDNFProtein2668 (RefSeq)
GFRA1ProteinNP_005255.1 (RefSeq)
GFRA2ProteinNP_001486.4 (RefSeq)
GFRA3ProteinNP_001487.2 (RefSeq)
GRB10ProteinNP_001357938.1 (RefSeq)
GRB2ProteinNP_002077.1 (RefSeq)
GRB7ProteinNP_001229371.2 (RefSeq)
GSK3BProteinNP_002084.2 (RefSeq)
HIF1AProteinNP_001521.1 (RefSeq)
HSPB1ProteinNP_001531.1 (RefSeq)
IKBKBProteinNP_001547.1 (RefSeq)
IP3Metabolite439456 (PubChem-compound)
ITGA3ProteinNP_002195.1 (RefSeq)
ITGA5Rna3678 (RefSeq)
ITGA5ProteinNP_002196.4 (RefSeq)
ITGA6ProteinNP_001073286.1 (RefSeq)
ITGB1ProteinNP_002202.2 (RefSeq)
ITGB3Rna3690 (RefSeq)
ITGB3ProteinNP_000203.2 (RefSeq)
ITPR1ProteinNP_001161744.1 (RefSeq)
ITPR2ProteinNP_002214.2 (RefSeq)
ITPR3ProteinNP_002215.2 (RefSeq)
KCND2ProteinNP_036413.1 (RefSeq)
LHX1ProteinNP_005559.2 (RefSeq)
LIFRna3976 (RefSeq)
LRIG1ProteinNP_056356.2 (RefSeq)
LYNProteinNP_002341.1 (RefSeq)
MAP2K1ProteinNP_002746.1 (RefSeq)
MAP2K2ProteinNP_109587.1 (RefSeq)
MAP2K5ProteinNP_660143.1 (RefSeq)
MAP3K14ProteinNP_003945.2 (RefSeq)
MAP3K3ProteinNP_976226.1 (RefSeq)
MAPK14ProteinNP_001306.1 (RefSeq)
MAPK1ProteinNP_002736.3 (RefSeq)
MAPK3ProteinNP_002737.2 (RefSeq)
MAPK7ProteinNP_620602.2 (RefSeq)
MAPK8ProteinNP_620637.1 (RefSeq)
MAPK9ProteinNP_002743.3 (RefSeq)
MEF2CProteinNP_002388.2 (RefSeq)
METProteinNP_001120972.1 (RefSeq)
MTORProteinNP_004949.1 (RefSeq)
MYCNProteinNP_001280157.1 (RefSeq)
MYCProteinNP_002458.2 (RefSeq)
MonosialotetrahexosylgangliosideMetabolite5497107 (PubChem-compound)
NANOS2Rna339345 (RefSeq)
NCAM1ProteinNP_001229536.1 (RefSeq)
NCK1ProteinNP_006144.1 (RefSeq)
NCS1ProteinNP_055101.2 (RefSeq)
NFKB2ProteinNP_001070962.1 (RefSeq)
NFKBIAProteinNP_065390.1 (RefSeq)
NRASProteinNP_002515.1 (RefSeq)
PCDHA4ProteinNP_061730.1 (RefSeq)
PCDHGB7ProteinNP_061750.1 (RefSeq)
PDLIM7ProteinNP_005442.2 (RefSeq)
PDPK1ProteinNP_002604.1 (RefSeq)
PGRRna5241 (RefSeq)
PIK3CBProteinNP_006210.1 (RefSeq)
PIK3R1ProteinNP_852664.1 (RefSeq)
PIP2Metabolite24742074 (PubChem-compound)
PIP3Metabolite101362114 (PubChem-compound)
PLCG1ProteinNP_002651.2 (RefSeq)
PLCG2ProteinNP_002652.2 (RefSeq)
POU1F1Rna5449 (RefSeq)
PPARGRna5468 (RefSeq)
PPARGC1ARna10891 (RefSeq)
PRKACAProteinNP_001291278.1 (RefSeq)
PRKAR2AProteinNP_001308911.1 (RefSeq)
PTENProteinNP_000305.3 (RefSeq)
PTK2ProteinNP_001339623.1 (RefSeq)
PTPN11ProteinNP_001317366.1 (RefSeq)
PXNProteinNP_001074324.1 (RefSeq)
RABEP1ProteinNP_004694.2 (RefSeq)
RAC1ProteinNP_061485.1 (RefSeq)
RAF1ProteinNP_001341618.1 (RefSeq)
RAP1AProteinNP_001010935.1 (RefSeq)
RAP1GAPProteinNP_001317312.1 (RefSeq)
RASA1ProteinNP_002881.1 (RefSeq)
RELAProteinNP_068810.3 (RefSeq)
RETProteinNP_066124.1 (RefSeq)
RHOAProteinNP_001655.1 (RefSeq)
ROCK1ProteinNP_005397.1 (RefSeq)
ROCK2ProteinNP_004841.2 (RefSeq)
RPS6KB1ProteinNP_001258971.1 (RefSeq)
RPTORProteinNP_065812.1 (RefSeq)
S1PR1ProteinNP_001391.2 (RefSeq)
S1PR3ProteinNP_005217.2 (RefSeq)
SH2B2ProteinNP_001346157.1 (RefSeq)
SHC1ProteinNP_001123512.1 (RefSeq)
SLC1A2Rna6506 (RefSeq)
SLC1A3Rna6507 (RefSeq)
SLC6A3ProteinNP_001035.1 (RefSeq)
SMAD2ProteinNP_001003652.1 (RefSeq)
SMAD3ProteinNP_005893.1 (RefSeq)
SORL1ProteinNP_003096.2 (RefSeq)
SP1ProteinNP_612482.2 (RefSeq)
SPHK1ProteinNP_892010.2 (RefSeq)
SPRY2ProteinNP_005833.1 (RefSeq)
SRCProteinNP_005408.1 (RefSeq)
SREBF1Rna6720 (RefSeq)
ST3GAL1Rna6482 (Entrez Gene)
ST3GAL1ProteinNP_003024.1 (RefSeq)
SYN1ProteinNP_008881.2 (RefSeq)
SYPProteinNP_003170.1 (RefSeq)
Sphingosine- 1-PhosphateMetabolite5283560 (PubChem-compound)
SphingosineMetabolite5280335 (PubChem-compound)
TFF1Rna7031 (RefSeq)
TGFBR1ProteinNP_001293139.1 (RefSeq)
THRna7054 (RefSeq)
TOP2ARna7153 (RefSeq)
VAV2ProteinNP_001127870.1 (RefSeq)
VEGFAProteinNP_003367.4 (RefSeq)
YES1ProteinNP_005424.1 (RefSeq)
YWHAZProteinNP_663723.1 (RefSeq)

Annotated Interactions

No annotated interactions

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