Netrin-1 signaling (Homo sapiens)

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1, 8514233, 74, 12, 186, 11, 13, 16, 251512, 22141961516, 2519143, 4, 2111, 132, 269, 10, 17, 24cytosolp-Y397-PTK2 FYN ATPDAGsTRPC6 HFE2 Netrin-1:pDCCdimer:pFAK:Src/FynTRPC1 p-5Y-UNC5C DCC:Ezrin complexGTPMAPK12 NTN1 NEO1 NTN1 TRPC7 Myosin-X:DCC/NeogeninNTN1 Netrin-1:DCC:UNC5CNTN1 WASL FYN p-Y397-PTK2 RGMB AGAP2Rho GEFs DOCK andTRIONetrin-1:DCC:pFyn:Nck:Rac1-GTP:AblimFADK1:DCColigomer:NetrinPI(4,5)P2p-Y397-PTK2 ATPHFE2 ROBO1 UNC5D ATPSRC-1 PTPN11SIAH2 NTN1 GTP NEO1 SRC-1 UNC5C SLIT1 p-Y397-PTK2 ATPSRC-1 GDPPI(4,5)P2 SRC-1 Active Cdc42 boundto Netrin:DCCcomplexUNC5B SRC-1 p-Y90,T538,S676,S695-PRKCQpEzrin:PIP2NEO1 TRIO ADPDSCAM:DCCUNC5B Netrin-1:NeogeninADPTRPC5 RGMB GTP NTN1 GTP RGMA PTPN11 SRC-1 I(1,4,5)P3DOCK1 CDC42 NTN1 DSCAM/DSCAML1homodimersActive Rac1 bound toNetrin-1-DCCcomplexp-Y1420-DCC DSCAM p-Y397-PTK2 Netrin-1:DCColigomer:pFADK1Netrin1:pUnc5C:DCC:Shp2NTN1 AGAP2 RGMA DCC, UNC5ANTN1 p-Y1420-DCC Netrin-1:pDCColigomer:pFAK:Fyn:NCK1Robo:SlitDSCAMNetrin:DCC:Nck:Cdc42-GTP:Active N-WASP:PIP2PLCG1DCC p-Y397-PTK2 p-T,Y-MAPK8p-Y1420-DCC p-Y397-PTK2 SRC-1 RAC1 SRC-1 p-T567-EZR TRPC1 SIAH1 bound toDCC:Netrin-1FYN PI(4,5)P2DCC bound toUNC-5:Netrin-1UNC5A p-Y397-PTK2 Netrin:DCC oligomerRAC1:GDPGTP DCC ABLIM3 NTN1 Netrin:DCC:PITPNCK1GTPGDPUNC5B NTN1 UNC5A DCC/NeogeninDSCAM:p-S144-PAK1:RAC1:GTPPI(4,5)P2 ADPCDC42:GDPRAC1 p-Y397-PTK2 ADPPITPNA NTN1 DOCK1 FYN DCC:Netrin-1SIAH1ADPPhospho-MAP kinasep38 (Mg2+ cofactor)UNC-5 receptorsUNC5A DCC ADPp-Y1420-DCC TRPC3(1-848) TRIO NTN1 NTN4TRPC channelsPI(4,5)P2NCK1 DCC ABLIM2 DCC NCK1 RAC1 p-T567-EZR DCC DCC TRIO CDC42 MAPK8DCC MYO10 Netrin:DCColigomer:pFAK:Fyn:Nck-1:Rho GEFs DOCK/Triop-Y-PLCG1 SRC-1 ABLIM1 TRPC7 p-Y1420-DCC DCC DSCAM MAPK13 FYN SIAH2 bound toDCC:Netrin-1NCK1 PITPNAMAPK14 UNC5C GTP FYN UNC5A NTN1 ABLIMMg2+ PTK2 DOCK1 TRPC5 p-Y146,Y354-EZR PI(4,5)P2 SLIT2(31-1529) DCC FYN p-Y397-PTK2 CDC42 N-WASPTRIO H2ONEO1SRC-1 NTN1 DSCAM RAC1 p-Y1420-DCC DSCAM, DSCAML1FYN ABLIM2 UNC5A MYO10NTN4 SLIT2(31-1529) SRC-1p-Y397-PTK2 PI(4,5)P2ABLIM1 p-Y146,Y354-EZRNTN1 ROBO1 TRIO p-Y1420-DCC pPLCgamma:PIP2TRPC3(1-848) SRC,FYNTRPC6 PI(4,5)P2 PI(4,5)P2 p-Y1420-DCC SRC-1 TRPC4 ATPSIAH2PIKE-L:UNC5BNetrin-1:DCC:pUNC5CFYN SRC-1 DCC DOCK1 DSCAM NTN1 SIAH1 UNC5B MAPK11 Activated TRPchannelsATPNTN1NTN1 UNC5C NCK1 FYN DSCAM:netrinp-S144-PAK1 GDP SLIT3 FYN DCC&UNC5A:Netrin-4NTN1 NEO1 p-S144-PAK1 UNC5D Ezrin:PIP2GDP ADPNTN1 NTN1 ABLIM3 FYN MAP kinase p38 (Mg2+cofactor)DCC DSCAML1 p-5Y-UNC5C SLIT3 DCCDSCAM PTK2SLIT1 p-T180,Y182-MAPK14 NCK1 UNC-5:Netrin-1complexTRPC4 DCC UNC5C p-T180,Y182-MAPK11 Neogenin:RGDNetrin1:DCColigomer:pFADK1:Fyn/srcUNC5BMg2+ p-Y1420-DCC GTP ATPDOCK1 DCC p-S144-PAK1:RAC1:GTPDSCAML1 UNC5D DOCK1 p-Y1420-DCC p-Y397-PTK2 TRIO DCC RGDRAC1 NCK1 DCC NTN1 DCC:Robo:Slit20


Description

Netrins are secreted proteins that play a crucial role in neuronal migration and in axon guidance during the development of the nervous system. To date, several Netrins have been described in mouse and humans: Netrin-1, -3/NTL2, -4/h and G-Netrins. Netrin-1 is the most studied member of the family and has been shown to play a crucial role in neuronal navigation during nervous system development mainly through its interaction with its receptors DCC and UNC5. Members of the Deleted in colorectal cancer (DCC) family- which includes DCC and Neogenin in vertebrates- mediate netrin-induced axon attraction, whereas the C. elegans UNC5 receptor and its four vertebrate homologs Unc5a-Unc5d mediate repulsion. View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 373752
Reactome-version 
Reactome version: 61
Reactome Author 
Reactome Author: Garapati, Phani Vijay

Quality Tags

Ontology Terms

 

Bibliography

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  1. Ren XR, Hong Y, Feng Z, Yang HM, Mei L, Xiong WC.; ''Tyrosine phosphorylation of netrin receptors in netrin-1 signaling.''; PubMed Europe PMC Scholia
  2. Stein E, Zou Y, Poo M, Tessier-Lavigne M.; ''Binding of DCC by netrin-1 to mediate axon guidance independent of adenosine A2B receptor activation.''; PubMed Europe PMC Scholia
  3. Hu G, Fearon ER.; ''Siah-1 N-terminal RING domain is required for proteolysis function, and C-terminal sequences regulate oligomerization and binding to target proteins.''; PubMed Europe PMC Scholia
  4. Fuerst PG, Koizumi A, Masland RH, Burgess RW.; ''Neurite arborization and mosaic spacing in the mouse retina require DSCAM.''; PubMed Europe PMC Scholia
  5. Meyerhardt JA, Caca K, Eckstrand BC, Hu G, Lengauer C, Banavali S, Look AT, Fearon ER.; ''Netrin-1: interaction with deleted in colorectal cancer (DCC) and alterations in brain tumors and neuroblastomas.''; PubMed Europe PMC Scholia
  6. Li X, Meriane M, Triki I, Shekarabi M, Kennedy TE, Larose L, Lamarche-Vane N.; ''The adaptor protein Nck-1 couples the netrin-1 receptor DCC (deleted in colorectal cancer) to the activation of the small GTPase Rac1 through an atypical mechanism.''; PubMed Europe PMC Scholia
  7. Agarwala KL, Nakamura S, Tsutsumi Y, Yamakawa K.; ''Down syndrome cell adhesion molecule DSCAM mediates homophilic intercellular adhesion.''; PubMed Europe PMC Scholia
  8. Yamagata M, Sanes JR.; ''Dscam and Sidekick proteins direct lamina-specific synaptic connections in vertebrate retina.''; PubMed Europe PMC Scholia
  9. Millard TH, Sharp SJ, Machesky LM.; ''Signalling to actin assembly via the WASP (Wiskott-Aldrich syndrome protein)-family proteins and the Arp2/3 complex.''; PubMed Europe PMC Scholia
  10. Meriane M, Tcherkezian J, Webber CA, Danek EI, Triki I, McFarlane S, Bloch-Gallego E, Lamarche-Vane N.; ''Phosphorylation of DCC by Fyn mediates Netrin-1 signaling in growth cone guidance.''; PubMed Europe PMC Scholia
  11. Agarwala KL, Ganesh S, Tsutsumi Y, Suzuki T, Amano K, Yamakawa K.; ''Cloning and functional characterization of DSCAML1, a novel DSCAM-like cell adhesion molecule that mediates homophilic intercellular adhesion.''; PubMed Europe PMC Scholia
  12. Bretscher A, Edwards K, Fehon RG.; ''ERM proteins and merlin: integrators at the cell cortex.''; PubMed Europe PMC Scholia
  13. Li W, Guan KL.; ''The Down syndrome cell adhesion molecule (DSCAM) interacts with and activates Pak.''; PubMed Europe PMC Scholia
  14. Barallobre MJ, Pascual M, Del Río JA, Soriano E.; ''The Netrin family of guidance factors: emphasis on Netrin-1 signalling.''; PubMed Europe PMC Scholia
  15. Martín M, Simon-Assmann P, Kedinger M, Martin M, Mangeat P, Real FX, Fabre M.; ''DCC regulates cell adhesion in human colon cancer derived HT-29 cells and associates with ezrin.''; PubMed Europe PMC Scholia
  16. Briançon-Marjollet A, Ghogha A, Nawabi H, Triki I, Auziol C, Fromont S, Piché C, Enslen H, Chebli K, Cloutier JF, Castellani V, Debant A, Lamarche-Vane N.; ''Trio mediates netrin-1-induced Rac1 activation in axon outgrowth and guidance.''; PubMed Europe PMC Scholia
  17. Li X, Gao X, Liu G, Xiong W, Wu J, Rao Y.; ''Netrin signal transduction and the guanine nucleotide exchange factor DOCK180 in attractive signaling.''; PubMed Europe PMC Scholia
  18. Shekarabi M, Kennedy TE.; ''The netrin-1 receptor DCC promotes filopodia formation and cell spreading by activating Cdc42 and Rac1.''; PubMed Europe PMC Scholia
  19. Qin S, Yu L, Gao Y, Zhou R, Zhang C.; ''Characterization of the receptors for axon guidance factor netrin-4 and identification of the binding domains.''; PubMed Europe PMC Scholia
  20. Li W, Lee J, Vikis HG, Lee SH, Liu G, Aurandt J, Shen TL, Fearon ER, Guan JL, Han M, Rao Y, Hong K, Guan KL.; ''Activation of FAK and Src are receptor-proximal events required for netrin signaling.''; PubMed Europe PMC Scholia
  21. Strübing C, Krapivinsky G, Krapivinsky L, Clapham DE.; ''Formation of novel TRPC channels by complex subunit interactions in embryonic brain.''; PubMed Europe PMC Scholia
  22. Liu G, Beggs H, Jürgensen C, Park HT, Tang H, Gorski J, Jones KR, Reichardt LF, Wu J, Rao Y.; ''Netrin requires focal adhesion kinase and Src family kinases for axon outgrowth and attraction.''; PubMed Europe PMC Scholia
  23. Rohatgi R, Ho HY, Kirschner MW.; ''Mechanism of N-WASP activation by CDC42 and phosphatidylinositol 4, 5-bisphosphate.''; PubMed Europe PMC Scholia
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  25. Cooper HM, Gad JM, Keeling SL.; ''The Deleted in Colorectal Cancer netrin guidance system: a molecular strategy for neuronal navigation.''; PubMed Europe PMC Scholia
  26. Moore SW, Tessier-Lavigne M, Kennedy TE.; ''Netrins and their receptors.''; PubMed Europe PMC Scholia
  27. Shekarabi M, Moore SW, Tritsch NX, Morris SJ, Bouchard JF, Kennedy TE.; ''Deleted in colorectal cancer binding netrin-1 mediates cell substrate adhesion and recruits Cdc42, Rac1, Pak1, and N-WASP into an intracellular signaling complex that promotes growth cone expansion.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
101460view11:32, 1 November 2018ReactomeTeamreactome version 66
100998view21:11, 31 October 2018ReactomeTeamreactome version 65
100534view19:45, 31 October 2018ReactomeTeamreactome version 64
100081view16:30, 31 October 2018ReactomeTeamreactome version 63
99632view15:02, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99238view12:44, 31 October 2018ReactomeTeamreactome version 62
93774view13:35, 16 August 2017ReactomeTeamreactome version 61
93301view11:19, 9 August 2017ReactomeTeamreactome version 61
88041view13:37, 25 July 2016RyanmillerOntology Term : 'signaling pathway pertinent to the brain and nervous system' added !
88040view13:37, 25 July 2016RyanmillerOntology Term : 'signaling pathway' added !
86384view09:16, 11 July 2016ReactomeTeamreactome version 56
83269view10:36, 18 November 2015ReactomeTeamVersion54
81379view12:54, 21 August 2015ReactomeTeamVersion53
76847view08:07, 17 July 2014ReactomeTeamFixed remaining interactions
76551view11:53, 16 July 2014ReactomeTeamFixed remaining interactions
75884view09:54, 11 June 2014ReactomeTeamRe-fixing comment source
75584view10:42, 10 June 2014ReactomeTeamReactome 48 Update
74939view13:46, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74583view08:37, 30 April 2014ReactomeTeamReactome46
42086view21:55, 4 March 2011MaintBotAutomatic update
39894view05:55, 21 January 2011MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ABLIM1 ProteinO14639 (Uniprot-TrEMBL)
ABLIM2 ProteinQ6H8Q1 (Uniprot-TrEMBL)
ABLIM3 ProteinO94929 (Uniprot-TrEMBL)
ABLIMComplexR-HSA-418808 (Reactome)
ADPMetaboliteCHEBI:16761 (ChEBI)
AGAP2 ProteinQ99490 (Uniprot-TrEMBL)
AGAP2ProteinQ99490 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:15422 (ChEBI)
Activated TRP channelsComplexR-HSA-622374 (Reactome)
Active Cdc42 bound

to Netrin:DCC

complex
ComplexR-HSA-418820 (Reactome)
Active Rac1 bound