IntAct European Bioinformatics Institute IntAct intact http://www.ebi.ac.uk/ http://www.ebi.ac.uk/intact/query/${ac} EBI-[0-9]+|IA:[0-9]+ INTerAction database (IntAct) provides an open source database and toolkit for the storage, presentation and analysis of molecular interactions. http://www.ebi.ac.uk/intact European Bioinformatics Institute; Wellcome Trust Genome Campus; Hinxton, Cambridge; CB10 1SD; United Kingdom http://www.ebi.ac.uk/intact/ Effective suppression of vascular network formation by combination of antibodies blocking VEGFR ligand binding and receptor dimerization. Effective suppression of vascular network formation by combination of antibodies blocking VEGFR ligand binding and receptor dimerization. Cancer Cell (1535-6108) 2010 imex curation Tvorogov D., Anisimov A., Zheng W., Leppanen VM., Tammela T., Laurinavicius S., Holnthoner W., Helotera H., Holopainen T., Jeltsch M., Kalkkinen N., Lankinen H., Ojala PM., Alitalo K. Cancer - Interactions investigated in the context of cancer Antibody-mediated inhibition of VEGF-C binding to VEGFR-3. Details of molecules provided by authors. kari.alitalo@helsinki.fi 06-April-2011: Contacted by JYOTI. orchard Only protein-protein interactions human-endothelium Homo sapiens endothelail cells/endothelium endothelium Endothelial cells [endothelium] anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Tvorogov D., Anisimov A., Zheng W., Leppanen VM., Tammela T., Laurinavicius S., Holnthoner W., Helotera H., Holopainen T., Jeltsch M., Kalkkinen N., Lankinen H., Ojala PM., Alitalo K. Cancer - Interactions investigated in the context of cancer Antibody-mediated inhibition of VEGF-C binding to VEGFR-3. Antibody-mediated inhibition of VEGF-C binding to VEGFR-3. Antibody-mediated inhibition of VEGF-C binding to VEGFR-3. Details of molecules provided by authors. kari.alitalo@helsinki.fi Accepted 2011-FEB-09 by ORCHARD 06-April-2011: Contacted by JYOTI. Cancer Cell (1535-6108) 2010 orchard Only protein-protein interactions imex curation Effective suppression of vascular network formation by combination of antibodies blocking VEGFR ligand binding and receptor dimerization. Effective suppression of vascular network formation by combination of antibodies blocking VEGFR ligand binding and receptor dimerization. Cancer Cell (1535-6108) 2010 imex curation Tvorogov D., Anisimov A., Zheng W., Leppanen VM., Tammela T., Laurinavicius S., Holnthoner W., Helotera H., Holopainen T., Jeltsch M., Kalkkinen N., Lankinen H., Ojala PM., Alitalo K. Cancer - Interactions investigated in the context of cancer Antibody-mediated inhibition of VEGF-C binding to VEGFR-3. Details of molecules provided by authors. kari.alitalo@helsinki.fi 06-April-2011: Contacted by JYOTI. orchard Only protein-protein interactions in vitro In vitro solid phase assay solid phase assay predetermined predetermined participant predetermined Tvorogov D., Anisimov A., Zheng W., Leppanen VM., Tammela T., Laurinavicius S., Holnthoner W., Helotera H., Holopainen T., Jeltsch M., Kalkkinen N., Lankinen H., Ojala PM., Alitalo K. Cancer - Interactions investigated in the context of cancer Antibody-mediated inhibition of VEGF-C binding to VEGFR-3. Antibody-mediated inhibition of VEGF-C binding to VEGFR-3. Details of molecules provided by authors. kari.alitalo@helsinki.fi Accepted 2011-FEB-09 by ORCHARD 06-April-2011: Contacted by JYOTI. Cancer Cell (1535-6108) 2010 orchard Only protein-protein interactions imex curation Effective suppression of vascular network formation by combination of antibodies blocking VEGFR ligand binding and receptor dimerization. Effective suppression of vascular network formation by combination of antibodies blocking VEGFR ligand binding and receptor dimerization. Cancer Cell (1535-6108) 2010 imex curation Tvorogov D., Anisimov A., Zheng W., Leppanen VM., Tammela T., Laurinavicius S., Holnthoner W., Helotera H., Holopainen T., Jeltsch M., Kalkkinen N., Lankinen H., Ojala PM., Alitalo K. Cancer - Interactions investigated in the context of cancer Antibody-mediated inhibition of VEGF-C binding to VEGFR-3. Details of molecules provided by authors. kari.alitalo@helsinki.fi 06-April-2011: Contacted by JYOTI. orchard Only protein-protein interactions in vitro In vitro solid phase assay solid phase assay western blot western blot Immuno blot Immuno blot Tvorogov D., Anisimov A., Zheng W., Leppanen VM., Tammela T., Laurinavicius S., Holnthoner W., Helotera H., Holopainen T., Jeltsch M., Kalkkinen N., Lankinen H., Ojala PM., Alitalo K. Cancer - Interactions investigated in the context of cancer Antibody-mediated inhibition of VEGF-C binding to VEGFR-3. Details of molecules provided by authors. kari.alitalo@helsinki.fi Accepted 2011-FEB-09 by ORCHARD 06-April-2011: Contacted by JYOTI. Cancer Cell (1535-6108) 2010 orchard Only protein-protein interactions imex curation vgfr3_human Vascular endothelial growth factor receptor 3 Tyrosine-protein kinase receptor FLT4 FLT4 Fms-like tyrosine kinase 4 VEGFR3 protein protein human Homo sapiens Human MQRGAALCLRLWLCLGLLDGLVSGYSMTPPTLNITEESHVIDTGDSLSISCRGQHPLEWAWPGAQEAPATGDKDSEDTGVVRDCEGTDARPYCKVLLLHEVHANDTGSYVCYYKYIKARIEGTTAASSYVFVRDFEQPFINKPDTLLVNRKDAMWVPCLVSIPGLNVTLRSQSSVLWPDGQEVVWDDRRGMLVSTPLLHDALYLQCETTWGDQDFLSNPFLVHITGNELYDIQLLPRKSLELLVGEKLVLNCTVWAEFNSGVTFDWDYPGKQAERGKWVPERRSQQTHTELSSILTIHNVSQHDLGSYVCKANNGIQRFRESTEVIVHENPFISVEWLKGPILEATAGDELVKLPVKLAAYPPPEFQWYKDGKALSGRHSPHALVLKEVTEASTGTYTLALWNSAAGLRRNISLELVVNVPPQIHEKEASSPSIYSRHSRQALTCTAYGVPLPLSIQWHWRPWTPCKMFAQRSLRRRQQQDLMPQCRDWRAVTTQDAVNPIESLDTWTEFVEGKNKTVSKLVIQNANVSAMYKCVVSNKVGQDERLIYFYVTTIPDGFTIESKPSEELLEGQPVLLSCQADSYKYEHLRWYRLNLSTLHDAHGNPLLLDCKNVHLFATPLAASLEEVAPGARHATLSLSIPRVAPEHEGHYVCEVQDRRSHDKHCHKKYLSVQALEAPRLTQNLTDLLVNVSDSLEMQCLVAGAHAPSIVWYKDERLLEEKSGVDLADSNQKLSIQRVREEDAGRYLCSVCNAKGCVNSSASVAVEGSEDKGSMEIVILVGTGVIAVFFWVLLLLIFCNMRRPAHADIKTGYLSIIMDPGEVPLEEQCEYLSYDASQWEFPRERLHLGRVLGYGAFGKVVEASAFGIHKGSSCDTVAVKMLKEGATASEHRALMSELKILIHIGNHLNVVNLLGACTKPQGPLMVIVEFCKYGNLSNFLRAKRDAFSPCAEKSPEQRGRFRAMVELARLDRRRPGSSDRVLFARFSKTEGGARRASPDQEAEDLWLSPLTMEDLVCYSFQVARGMEFLASRKCIHRDLAARNILLSESDVVKICDFGLARDIYKDPDYVRKGSARLPLKWMAPESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGVQINEEFCQRLRDGTRMRAPELATPAIRRIMLNCWSGDPKARPAFSELVEILGDLLQGRGLQEEEEVCMAPRSSQSSEEGSFSQVSTMALHIAQADAEDSPPSLQRHSLAARYYNWVSFPGCLARGAETRGSSRMKTFEEFPMTPTTYKGSVDNQTDSGMVLASEEFEQIESRHRQESGFSCKGPGQNVAVTRAHPDSQGRRRRPERGARGGQVFYNSEYGELSEPSEEDHCSPSARVTFFTDNSY DIP protein P35916 original sequence version: 173 B1473AAAC95E7E93 vegfc_human Vascular endothelial growth factor C VEGFC Flt4 ligand Vascular endothelial growth factor-related protein protein protein human Homo sapiens Human MHLLGFFSVACSLLAAALLPGPREAPAAAAAFESGLDLSDAEPDAGEATAYASKDLEEQLRSVSSVDELMTVLYPEYWKMYKCQLRKGGWQHNREQANLNSRTEETIKFAAAHYNTEILKSIDNEWRKTQCMPREVCIDVGKEFGVATNTFFKPPCVSVYRCGGCCNSEGLQCMNTSTSYLSKTLFEITVPLSQGPKPVTISFANHTSCRCMSKLDVYRQVHSIIRRSLPATLPQCQAANKTCPTNYMWNNHICRCLAQEDFMFSSDAGDDSTDGFHDICGPNKELDEETCQCVCRAGLRPASCGPHKELDRNSCQCVCKNKLFPSQCGANREFDENTCQCVCKRTCPRNQPLNPGKCACECTESPQKCLLKGKKFHHQTCSCYRRPCTNRQKACEPGFSYSEEVCRCVPSYWKRPQMS DIP protein P49767 original sequence version: 98 9F598719DB3E014F vgfr2_human Vascular endothelial growth factor receptor 2 Kinase insert domain receptor Protein-tyrosine kinase receptor flk-1 KDR FLK1 Fetal liver kinase 1 VEGFR2 protein protein human Homo sapiens Human MQSKVLLAVALWLCVETRAASVGLPSVSLDLPRLSIQKDILTIKANTTLQITCRGQRDLDWLWPNNQSGSEQRVEVTECSDGLFCKTLTIPKVIGNDTGAYKCFYRETDLASVIYVYVQDYRSPFIASVSDQHGVVYITENKNKTVVIPCLGSISNLNVSLCARYPEKRFVPDGNRISWDSKKGFTIPSYMISYAGMVFCEAKINDESYQSIMYIVVVVGYRIYDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKPFVAFGSGMESLVEATVGERVRIPAKYLGYPPPEIKWYKNGIPLESNHTIKAGHVLTIMEVSERDTGNYTVILTNPISKEKQSHVVSLVVYVPPQIGEKSLISPVDSYQYGTTQTLTCTVYAIPPPHHIHWYWQLEEECANEPSQAVSVTNPYPCEEWRSVEDFQGGNKIEVNKNQFALIEGKNKTVSTLVIQAANVSALYKCEAVNKVGRGERVISFHVTRGPEITLQPDMQPTEQESVSLWCTADRSTFENLTWYKLGPQPLPIHVGELPTPVCKNLDTLWKLNATMFSNSTNDILIMELKNASLQDQGDYVCLAQDRKTKKRHCVVRQLTVLERVAPTITGNLENQTTSIGESIEVSCTASGNPPPQIMWFKDNETLVEDSGIVLKDGNRNLTIRRVRKEDEGLYTCQACSVLGCAKVEAFFIIEGAQEKTNLEIIILVGTAVIAMFFWLLLVIILRTVKRANGGELKTGYLSIVMDPDELPLDEHCERLPYDASKWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCRTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVNLLGACTKPGGPLMVIVEFCKFGNLSTYLRSKRNEFVPYKTKGARFRQGKDYVGAIPVDLKRRLDSITSSQSSASSGFVEEKSLSDVEEEEAPEDLYKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHGEPSQRPTFSELVEHLGNLLQANAQQDGKDYIVLPISETLSMEEDSGLSLPTSPVSCMEEEEVCDPKFHYDNTAGISQYLQNSKRKSRPVSVKTFEDIPLEEPEVKVIPDDNQTDSGMVLASEELKTLEDRTKLSPSFGGMVPSKSRESVASEGSNQTSGYQSGYHSDDTDTTVYSSEEAELLKLIEIGVQTGSTAQILQPDSGTTLSSPPV DIP protein P35968 original sequence version: 81 DIP protein P35968 original sequence version: 146 DIP protein P35968 original sequence version: 117 DIP protein P35968 original sequence version: 121 59E7C44B05CFEBB3 vegfc-vegfr3 3 5 unspecified role unspecified role bait bait c_terminal his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range vegfc_mature sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain drome-schneider_2 Drosophila melanogaster late embryo cells Fruit fly schneider_2 Established from the late embryo of Drosophila melanogaster Mixture of diploid and tetraploid. Originally had some XY cells now predominantly XX. 4 unspecified role unspecified role prey prey region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain drome-schneider_2 Drosophila melanogaster late embryo cells Fruit fly schneider_2 Established from the late embryo of Drosophila melanogaster Mixture of diploid and tetraploid. Originally had some XY cells now predominantly XX. physical association physical association Fig 1C Unlike the 3C5 antibody, the 2E11 antibody did not block the binding of VEGFR-3 extracellular domain to immobilized VEGF-C. 3C5 antibody vegfc-flt4 2 5 unspecified role unspecified role bait bait vegfc_mature sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain c_terminal his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range drome-schneider_2 Drosophila melanogaster late embryo cells Fruit fly schneider_2 Established from the late embryo of Drosophila melanogaster Mixture of diploid and tetraploid. Originally had some XY cells now predominantly XX. 4 unspecified role unspecified role prey prey region alk phosphatase tag alkaline phosphatase tag alk phosphatase tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain mouse-3t3 Mus musculus embryo cells 3t3 Mouse embryo fibroblast cells physical association physical association Fig 1D Unlike the 3C5 antibody, the 2E11 antibody did not block the binding of VEGFR-3 extracellular domain to immobilized VEGF-C. flt4-kdr-2 1 4 unspecified role unspecified role bait bait 6 unspecified role unspecified role prey prey physical association physical association Fig 4A. VEGF-C Antibodies 2E11 and 3C5 inhibit the formation of VEGFR-2/VEGFR-3 heterodimers.