{"id":{"repo_id":"aachen","oai_identifier":"oai:publications.rwth-aachen.de:52652"},"canonical_url":"https://search.dev.ndltd.org/etd/aachen/oai:publications.rwth-aachen.de:52652","repository":{"repo_id":"aachen","name":"RWTH Aachen University","base_url":"https://publications.rwth-aachen.de/oai2d"},"display":{"title":"Das Tyrosin 759 des Signaltransduktors gp130 in der IL-6-abhängigen Proliferation von Prä-B-Zellen","abstract":"IL-6 signaltransduction requires a cytokine-receptor complex containing the signal transducing receptor subunit glycoprotein (gp) 130. Binding of IL-6 to its specific a-receptor induces dimerization of gp130, activation of th gp130-associated Janus kinases Jak1, Jak2 and Tyk2 and phosphorylation of gp130 at cytoplasmic tyrosine residues. These phosphotyrosines serve as docking sites for SH2-domain containing proteins such as STAT1, STAT3, the protein tyrosine phosphatase SHP2 and the feedback inhibitor SOCS3. SHP2 tyrosine phosphorylation is crucial for the activation of the Ras/Raf/MAPK pathway and thus proliferation and differentiation after IL-6 stimulation. Furthermore SHP2 is involved in negative regulation of the signal transduction through the Jak/STAT pathway. Negative regulation of IL-6 signal transduction through SHP2 and SOCS3 requires the tyrosine 759 of gp130. Interleukin-6 induces B-cell proliferation. There have been contradictory results in revealing essential factors and signaling pathways for proliferation depending on IL-6. We could recently demonstrate that the presence of a single STAT-recruitement site within gp130 is sufficient for IL-6 induced proliferation of Ba/F3 cells (Schmitz et al. (2000), J. Immunol. 164: 848-854). In clear contrast, the requirement of SHP2-activation for the proliferation of pre-B Ba/F3 cells has been reported using deleted chimere receptors (Fukada et al. (1996) Immunity, 5: 449-460). To unravel this discrepancy we analysed IL-6-induced dose-dependent proliferation of Ba/F3 cells through receptor complexes lacking the SHP2/SCS3 recruitment sites. Therefore murine pre-B-cells (Ba/F3 cells) that do not express endogenous gp130 were stable transfected with gp130 (Ba/F3-gp130) or a gp130 Y759F mutant lacking the tyrosine motif essential for the recruitement of SHP2 and SOCS3 (Ba/F3-gp130(Y759F)). As expected, after IL-6 stimulation there was neither SHP2 nor ERK1/2 phosphorylation apparent in cells expressing the mutated gp130 receptor. In contrast to the published data of Fukada et al. we observed IL-6-induced proliferation of pre-B-cells in the absence of SHP2 phosphorylation. Interestingly, Ba/F3 cells expressing gp130 receptor mutants lacking Y759 proliferate even much more efficient at low concentrations of IL-6 than cells expressing wild type gp130. Our data demonstrate that the tyrosine 759 of gp130 is not essential for IL-6-induced proliferation of transfected Ba/F3 cells but rather a mediator of inhibition of cell proliferation at low doses of IL-6. Therefore, SHP2 activation appears to be relevant for IL-6-induced proliferation only after stimulation with very large (unphysiological) amounts of IL-6 as used by Fukada et al.","abstract_html":"IL-6 signaltransduction requires a cytokine-receptor complex containing the signal transducing receptor subunit glycoprotein (gp) 130. Binding of IL-6 to its specific a-receptor induces dimerization of gp130, activation of th gp130-associated Janus kinases Jak1, Jak2 and Tyk2 and phosphorylation of gp130 at cytoplasmic tyrosine residues. These phosphotyrosines serve as docking sites for SH2-domain containing proteins such as STAT1, STAT3, the protein tyrosine phosphatase SHP2 and the feedback inhibitor SOCS3. SHP2 tyrosine phosphorylation is crucial for the activation of the Ras/Raf/MAPK pathway and thus proliferation and differentiation after IL-6 stimulation. Furthermore SHP2 is involved in negative regulation of the signal transduction through the Jak/STAT pathway. Negative regulation of IL-6 signal transduction through SHP2 and SOCS3 requires the tyrosine 759 of gp130. Interleukin-6 induces B-cell proliferation. There have been contradictory results in revealing essential factors and signaling pathways for proliferation depending on IL-6. We could recently demonstrate that the presence of a single STAT-recruitement site within gp130 is sufficient for IL-6 induced proliferation of Ba/F3 cells (Schmitz et al. (2000), J. Immunol. 164: 848-854). In clear contrast, the requirement of SHP2-activation for the proliferation of pre-B Ba/F3 cells has been reported using deleted chimere receptors (Fukada et al. (1996) Immunity, 5: 449-460). To unravel this discrepancy we analysed IL-6-induced dose-dependent proliferation of Ba/F3 cells through receptor complexes lacking the SHP2/SCS3 recruitment sites. Therefore murine pre-B-cells (Ba/F3 cells) that do not express endogenous gp130 were stable transfected with gp130 (Ba/F3-gp130) or a gp130 Y759F mutant lacking the tyrosine motif essential for the recruitement of SHP2 and SOCS3 (Ba/F3-gp130(Y759F)). As expected, after IL-6 stimulation there was neither SHP2 nor ERK1/2 phosphorylation apparent in cells expressing the mutated gp130 receptor. In contrast to the published data of Fukada et al. we observed IL-6-induced proliferation of pre-B-cells in the absence of SHP2 phosphorylation. Interestingly, Ba/F3 cells expressing gp130 receptor mutants lacking Y759 proliferate even much more efficient at low concentrations of IL-6 than cells expressing wild type gp130. Our data demonstrate that the tyrosine 759 of gp130 is not essential for IL-6-induced proliferation of transfected Ba/F3 cells but rather a mediator of inhibition of cell proliferation at low doses of IL-6. Therefore, SHP2 activation appears to be relevant for IL-6-induced proliferation only after stimulation with very large (unphysiological) amounts of IL-6 as used by Fukada et al.","abstract_has_math":false,"creators":["Friederichs, Kerstin"],"institution":"Publikationsserver der RWTH Aachen University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Heinrich, Peter C."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2004,"date_issued":"2004","date_published":"2004","updated_at":"2026-07-30T19:41:00Z","subjects":["info:eu-repo/classification/ddc/610","Medizin","IL-6","SHP-2","SOCS3","gp130"],"languages":["ger"],"rights":["info:eu-repo/semantics/openAccess"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-114859%22"],"render_values":[{"text":"https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-114859%22","href":"https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-114859%22","code":true}]}]},"links":{"outbound_url":"https://publications.rwth-aachen.de/record/52652","outbound_label":"Repository record","outbound_source":"dc:identifier"},"source_record":{"url":"https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A52652","prefix":"oai_dc"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Heinrich, Peter C."]},{"key":"dc:creator","label":"Author","values":["Friederichs, Kerstin"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:coverage","label":"Dc Coverage","values":["DE"]},{"key":"dc:date","label":"Dc Date","values":["2004"]},{"key":"dc:publisher","label":"Institution","values":["Publikationsserver der RWTH Aachen University"]},{"key":"dc:relation","label":"Dc Relation","values":["info:eu-repo/semantics/altIdentifier/urn/urn:nbn:de:hbz:82-opus-10198"]},{"key":"dc:type","label":"Dc Type","values":["info:eu-repo/semantics/doctoralThesis","info:eu-repo/semantics/publishedVersion"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["info:eu-repo/classification/ddc/610","Medizin","IL-6","SHP-2","SOCS3","gp130"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["ger"]},{"key":"dc:rights","label":"Dc Rights","values":["info:eu-repo/semantics/openAccess"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://publications.rwth-aachen.de/record/52652","https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-114859%22"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["IL-6 signaltransduction requires a cytokine-receptor complex containing the signal transducing receptor subunit glycoprotein (gp) 130. Binding of IL-6 to its specific a-receptor induces dimerization of gp130, activation of th gp130-associated Janus kinases Jak1, Jak2 and Tyk2 and phosphorylation of gp130 at cytoplasmic tyrosine residues. These phosphotyrosines serve as docking sites for SH2-domain containing proteins such as STAT1, STAT3, the protein tyrosine phosphatase SHP2 and the feedback inhibitor SOCS3. SHP2 tyrosine phosphorylation is crucial for the activation of the Ras/Raf/MAPK pathway and thus proliferation and differentiation after IL-6 stimulation. Furthermore SHP2 is involved in negative regulation of the signal transduction through the Jak/STAT pathway. Negative regulation of IL-6 signal transduction through SHP2 and SOCS3 requires the tyrosine 759 of gp130. Interleukin-6 induces B-cell proliferation. There have been contradictory results in revealing essential factors and signaling pathways for proliferation depending on IL-6. We could recently demonstrate that the presence of a single STAT-recruitement site within gp130 is sufficient for IL-6 induced proliferation of Ba/F3 cells (Schmitz et al. (2000), J. Immunol. 164: 848-854). In clear contrast, the requirement of SHP2-activation for the proliferation of pre-B Ba/F3 cells has been reported using deleted chimere receptors (Fukada et al. (1996) Immunity, 5: 449-460). To unravel this discrepancy we analysed IL-6-induced dose-dependent proliferation of Ba/F3 cells through receptor complexes lacking the SHP2/SCS3 recruitment sites. Therefore murine pre-B-cells (Ba/F3 cells) that do not express endogenous gp130 were stable transfected with gp130 (Ba/F3-gp130) or a gp130 Y759F mutant lacking the tyrosine motif essential for the recruitement of SHP2 and SOCS3 (Ba/F3-gp130(Y759F)). As expected, after IL-6 stimulation there was neither SHP2 nor ERK1/2 phosphorylation apparent in cells expressing the mutated gp130 receptor. In contrast to the published data of Fukada et al. we observed IL-6-induced proliferation of pre-B-cells in the absence of SHP2 phosphorylation. Interestingly, Ba/F3 cells expressing gp130 receptor mutants lacking Y759 proliferate even much more efficient at low concentrations of IL-6 than cells expressing wild type gp130. Our data demonstrate that the tyrosine 759 of gp130 is not essential for IL-6-induced proliferation of transfected Ba/F3 cells but rather a mediator of inhibition of cell proliferation at low doses of IL-6. Therefore, SHP2 activation appears to be relevant for IL-6-induced proliferation only after stimulation with very large (unphysiological) amounts of IL-6 as used by Fukada et al."]},{"key":"dc:source","label":"Dc Source","values":["Aachen : Publikationsserver der RWTH Aachen University 75 S. : Ill., graph. Darst. (2004). = Aachen, Techn. Hochsch., Diss., 2004"]},{"key":"dc:title","label":"Title","values":["Das Tyrosin 759 des Signaltransduktors gp130 in der IL-6-abhängigen Proliferation von Prä-B-Zellen"]}]}],"canonical_facts":{"dc:contributor":["Heinrich, Peter C."],"dc:coverage":["DE"],"dc:creator":["Friederichs, Kerstin"],"dc:date":["2004"],"dc:description":["IL-6 signaltransduction requires a cytokine-receptor complex containing the signal transducing receptor subunit glycoprotein (gp) 130. Binding of IL-6 to its specific a-receptor induces dimerization of gp130, activation of th gp130-associated Janus kinases Jak1, Jak2 and Tyk2 and phosphorylation of gp130 at cytoplasmic tyrosine residues. These phosphotyrosines serve as docking sites for SH2-domain containing proteins such as STAT1, STAT3, the protein tyrosine phosphatase SHP2 and the feedback inhibitor SOCS3. SHP2 tyrosine phosphorylation is crucial for the activation of the Ras/Raf/MAPK pathway and thus proliferation and differentiation after IL-6 stimulation. Furthermore SHP2 is involved in negative regulation of the signal transduction through the Jak/STAT pathway. Negative regulation of IL-6 signal transduction through SHP2 and SOCS3 requires the tyrosine 759 of gp130. Interleukin-6 induces B-cell proliferation. There have been contradictory results in revealing essential factors and signaling pathways for proliferation depending on IL-6. We could recently demonstrate that the presence of a single STAT-recruitement site within gp130 is sufficient for IL-6 induced proliferation of Ba/F3 cells (Schmitz et al. (2000), J. Immunol. 164: 848-854). In clear contrast, the requirement of SHP2-activation for the proliferation of pre-B Ba/F3 cells has been reported using deleted chimere receptors (Fukada et al. (1996) Immunity, 5: 449-460). To unravel this discrepancy we analysed IL-6-induced dose-dependent proliferation of Ba/F3 cells through receptor complexes lacking the SHP2/SCS3 recruitment sites. Therefore murine pre-B-cells (Ba/F3 cells) that do not express endogenous gp130 were stable transfected with gp130 (Ba/F3-gp130) or a gp130 Y759F mutant lacking the tyrosine motif essential for the recruitement of SHP2 and SOCS3 (Ba/F3-gp130(Y759F)). As expected, after IL-6 stimulation there was neither SHP2 nor ERK1/2 phosphorylation apparent in cells expressing the mutated gp130 receptor. In contrast to the published data of Fukada et al. we observed IL-6-induced proliferation of pre-B-cells in the absence of SHP2 phosphorylation. Interestingly, Ba/F3 cells expressing gp130 receptor mutants lacking Y759 proliferate even much more efficient at low concentrations of IL-6 than cells expressing wild type gp130. Our data demonstrate that the tyrosine 759 of gp130 is not essential for IL-6-induced proliferation of transfected Ba/F3 cells but rather a mediator of inhibition of cell proliferation at low doses of IL-6. Therefore, SHP2 activation appears to be relevant for IL-6-induced proliferation only after stimulation with very large (unphysiological) amounts of IL-6 as used by Fukada et al."],"dc:identifier":["https://publications.rwth-aachen.de/record/52652","https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-114859%22"],"dc:language":["ger"],"dc:publisher":["Publikationsserver der RWTH Aachen University"],"dc:relation":["info:eu-repo/semantics/altIdentifier/urn/urn:nbn:de:hbz:82-opus-10198"],"dc:rights":["info:eu-repo/semantics/openAccess"],"dc:source":["Aachen : Publikationsserver der RWTH Aachen University 75 S. : Ill., graph. Darst. (2004). = Aachen, Techn. Hochsch., Diss., 2004"],"dc:subject":["info:eu-repo/classification/ddc/610","Medizin","IL-6","SHP-2","SOCS3","gp130"],"dc:title":["Das Tyrosin 759 des Signaltransduktors gp130 in der IL-6-abhängigen Proliferation von Prä-B-Zellen"],"dc:type":["info:eu-repo/semantics/doctoralThesis","info:eu-repo/semantics/publishedVersion"]},"updated_at":"2026-07-30T19:41:00Z"}