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/ Biochemical and functional analyses of gp130 mutants unveil JAK1 as a novel therapeutic target in human inflammatory hepatocellular adenoma. Biochemical and functional analyses of gp130 mutants unveil JAK1 as a novel therapeutic target in human inflammatory hepatocellular adenoma. Oncoimmunology 2013 imex curation Poussin K., Pilati C., Couchy G., Calderaro J., Bioulac-Sage P., Bacq Y., Paradis V., Leteurtre E., Sturm N., Ramos J., Guettier C., Bardier-Dupas A., Boulai A., Wendum D., Selves J., Izard T., Nault JC., Zucman-Rossi J. jessica.zucman-rossi@inserm.fr 09-May-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation human-hep_3b Homo sapiens hepatocellular carcinoma (HCC) cells (p53-null). hep_3b human hepatocellular carcinoma (HCC) cells (p53-null). anti tag coip anti tag coimmunoprecipitation anti tag coip anti tag western anti tag western blot anti tag western Poussin K., Pilati C., Couchy G., Calderaro J., Bioulac-Sage P., Bacq Y., Paradis V., Leteurtre E., Sturm N., Ramos J., Guettier C., Bardier-Dupas A., Boulai A., Wendum D., Selves J., Izard T., Nault JC., Zucman-Rossi J. jessica.zucman-rossi@inserm.fr Accepted 2018-SEP-20 AT 10:26 BST AT 10:26 BST by MARTA Oncoimmunology 2013 imex curation Biochemical and functional analyses of gp130 mutants unveil JAK1 as a novel therapeutic target in human inflammatory hepatocellular adenoma. Biochemical and functional analyses of gp130 mutants unveil JAK1 as a novel therapeutic target in human inflammatory hepatocellular adenoma. Oncoimmunology 2013 imex curation Poussin K., Pilati C., Couchy G., Calderaro J., Bioulac-Sage P., Bacq Y., Paradis V., Leteurtre E., Sturm N., Ramos J., Guettier C., Bardier-Dupas A., Boulai A., Wendum D., Selves J., Izard T., Nault JC., Zucman-Rossi J. jessica.zucman-rossi@inserm.fr 09-May-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation human-hep_3b Homo sapiens hepatocellular carcinoma (HCC) cells (p53-null). hep_3b human hepatocellular carcinoma (HCC) cells (p53-null). anti bait coip anti bait coimmunoprecipitation anti bait coip anti tag western anti tag western blot anti tag western Poussin K., Pilati C., Couchy G., Calderaro J., Bioulac-Sage P., Bacq Y., Paradis V., Leteurtre E., Sturm N., Ramos J., Guettier C., Bardier-Dupas A., Boulai A., Wendum D., Selves J., Izard T., Nault JC., Zucman-Rossi J. jessica.zucman-rossi@inserm.fr Accepted 2018-SEP-20 AT 10:26 BST AT 10:26 BST by MARTA Oncoimmunology 2013 imex curation osmr_human Oncostatin-M-specific receptor subunit beta OSMRB Interleukin-31 receptor subunit beta OSMR protein protein human Homo sapiens Human MALFAVFQTTFFLTLLSLRTYQSEVLAERLPLTPVSLKVSTNSTRQSLHLQWTVHNLPYHQELKMVFQIQISRIETSNVIWVGNYSTTVKWNQVLHWSWESELPLECATHFVRIKSLVDDAKFPEPNFWSNWSSWEEVSVQDSTGQDILFVFPKDKLVEEGTNVTICYVSRNIQNNVSCYLEGKQIHGEQLDPHVTAFNLNSVPFIRNKGTNIYCEASQGNVSEGMKGIVLFVSKVLEEPKDFSCETEDFKTLHCTWDPGTDTALGWSKQPSQSYTLFESFSGEKKLCTHKNWCNWQITQDSQETYNFTLIAENYLRKRSVNILFNLTHRVYLMNPFSVNFENVNATNAIMTWKVHSIRNNFTYLCQIELHGEGKMMQYNVSIKVNGEYFLSELEPATEYMARVRCADASHFWKWSEWSGQNFTTLEAAPSEAPDVWRIVSLEPGNHTVTLFWKPLSKLHANGKILFYNVVVENLDKPSSSELHSIPAPANSTKLILDRCSYQICVIANNSVGASPASVIVISADPENKEVEEERIAGTEGGFSLSWKPQPGDVIGYVVDWCDHTQDVLGDFQWKNVGPNTTSTVISTDAFRPGVRYDFRIYGLSTKRIACLLEKKTGYSQELAPSDNPHVLVDTLTSHSFTLSWKDYSTESQPGFIQGYHVYLKSKARQCHPRFEKAVLSDGSECCKYKIDNPEEKALIVDNLKPESFYEFFITPFTSAGEGPSATFTKVTTPDEHSSMLIHILLPMVFCVLLIMVMCYLKSQWIKETCYPDIPDPYKSSILSLIKFKENPHLIIMNVSDCIPDAIEVVSKPEGTKIQFLGTRKSLTETELTKPNYLYLLPTEKNHSGPGPCICFENLTYNQAASDSGSCGHVPVSPKAPSMLGLMTSPENVLKALEKNYMNSLGEIPAGETSLNYVSQLASPMFGDKDSLPTNPVEAPHCSEYKMQMAVSLRLALPPPTENSSLSSITLLDPGEHYC 179852CA3D90D9EF il6rb_human Interleukin-6 receptor subunit beta IL6ST Interleukin-6 signal transducer Membrane glycoprotein 130 CDw130 Oncostatin-M receptor subunit alpha protein protein human Homo sapiens Human MLTLQTWLVQALFIFLTTESTGELLDPCGYISPESPVVQLHSNFTAVCVLKEKCMDYFHVNANYIVWKTNHFTIPKEQYTIINRTASSVTFTDIASLNIQLTCNILTFGQLEQNVYGITIISGLPPEKPKNLSCIVNEGKKMRCEWDGGRETHLETNFTLKSEWATHKFADCKAKRDTPTSCTVDYSTVYFVNIEVWVEAENALGKVTSDHINFDPVYKVKPNPPHNLSVINSEELSSILKLTWTNPSIKSVIILKYNIQYRTKDASTWSQIPPEDTASTRSSFTVQDLKPFTEYVFRIRCMKEDGKGYWSDWSEEASGITYEDRPSKAPSFWYKIDPSHTQGYRTVQLVWKTLPPFEANGKILDYEVTLTRWKSHLQNYTVNATKLTVNLTNDRYLATLTVRNLVGKSDAAVLTIPACDFQATHPVMDLKAFPKDNMLWVEWTTPRESVKKYILEWCVLSDKAPCITDWQQEDGTVHRTYLRGNLAESKCYLITVTPVYADGPGSPESIKAYLKQAPPSKGPTVRTKKVGKNEAVLEWDQLPVDVQNGFIRNYTIFYRTIIGNETAVNVDSSHTEYTLSSLTSDTLYMVRMAAYTDEGGKDGPEFTFTTPKFAQGEIEAIVVPVCLAFLLTTLLGVLFCFNKRDLIKKHIWPNVPDPSKSHIAQWSPHTPPRHNFNSKDQMYSDGNFTDVSVVEIEANDKKPFPEDLKSLDLFKKEKINTEGHSSGIGGSSCMSSSRPSISSSDENESSQNTSSTVQYSTVVHSGYRHQVPSVQVFSRSESTQPLLDSEERPEDLQLVDHVDGGDGILPRQQYFKQNCSQHESSPDISHFERSKQVSSVNEEDFVRLKQQISDHISQSCGSGQMKMFQEVSAADAFGPGTEGQVERFETVGMEAATDEGMPKSYLPQTVRQGGYMPQ 6510A4409FFCF08C il6st-il6st-3 1 4 unspecified role unspecified role bait bait over-expressed over expressed level over-expressed flag tag flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged c-term range C-terminal range c-term range c-term range C-terminal range c-term range p.Ala418_Phe421del mutation causing mutation causing an interaction mutation enabling interaction mutation causing mutation causing an interaction certain certain sequence position certain certain certain sequence position certain ACDF . 4 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed myc tag myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range p.Ala418_Phe421del mutation causing mutation causing an interaction mutation enabling interaction mutation causing mutation causing an interaction certain certain sequence position certain certain certain sequence position certain ACDF . physical association physical association Fig. 3A As previously shown,5 wild-type gp130 do not homodimerize in the absence of IL-6. Conversely, IHCA-associated gp130 mutants are fully capable of homodimerizing as well as of heterodimerizing with wild-type gp130 in the absence of IL-6 (Fig. 3A). il6st-il6st-2 1 4 unspecified role unspecified role bait bait over-expressed over expressed level over-expressed flag tag flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged c-term range C-terminal range c-term range c-term range C-terminal range c-term range p.Tyr186_Tyr190del mutation causing mutation causing an interaction mutation enabling interaction mutation causing mutation causing an interaction certain certain sequence position certain certain certain sequence position certain YSTVY . 4 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed myc tag myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range p.Tyr186_Tyr190del mutation causing mutation causing an interaction mutation enabling interaction mutation causing mutation causing an interaction certain certain sequence position certain certain certain sequence position certain YSTVY . physical association physical association Fig. 3A As previously shown,5 wild-type gp130 do not homodimerize in the absence of IL-6. Conversely, IHCA-associated gp130 mutants are fully capable of homodimerizing as well as of heterodimerizing with wild-type gp130 in the absence of IL-6 (Fig. 3A). il6st-il6st-4 2 3 unspecified role unspecified role bait bait physiological level physiological level endogenous level endogenous endogenous endogenous level 4 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed flag tag flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged c-term range C-terminal range c-term range c-term range C-terminal range c-term range p.Tyr186_Tyr190del mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain YSTVY . physical association physical association Fig. 3D Gp130 also binds to the OSMR, an interaction that is required for OSMR signaling. As anticipated, the interaction between wild-type gp130 and OSMR in Hep3B cells required OSM, whereas gp130 mutants formed heterodimers with OSMR even in the absence of its ligand (Fig. 3D). osmr-il6st-1 2 3 unspecified role unspecified role bait bait physiological level physiological level endogenous level endogenous endogenous endogenous level 4 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed p.Tyr186_Tyr190del mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain YSTVY . flag tag flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged c-term range C-terminal range c-term range c-term range C-terminal range c-term range physical association physical association Fig. 3D Gp130 also binds to the OSMR, an interaction that is required for OSMR signaling. As anticipated, the interaction between wild-type gp130 and OSMR in Hep3B cells required OSM, whereas gp130 mutants formed heterodimers with OSMR even in the absence of its ligand (Fig. 3D). OSM ligand