{"id":{"repo_id":"lmu-germany","oai_identifier":"oai:edoc.ub.uni-muenchen.de:1235"},"canonical_url":"https://search.dev.ndltd.org/etd/lmu-germany/oai:edoc.ub.uni-muenchen.de:1235","repository":{"repo_id":"lmu-germany","name":"Ludwig Maxmilians Universität München","base_url":"https://edoc.ub.uni-muenchen.de/cgi/oai2"},"display":{"title":"Ras signaling enhances the activity of C/EBPalpha to induce granulocytic differentiation by phosphorylation of serine 248","abstract":"The transcription factor C/EBPa regulates early steps of normal granulocyte differentiation since mice with a disruption of the C/EBPa gene do not express detectable levels of the G-CSF receptor and produce no neutrophils. We have recently shown that C/EBPa function is also impaired in acute myeloid leukemias. However, how the transcriptional activity of C/EBPa is regulated both in myelopoiesis and leukemogenesis, is not fully understood. The current study demonstrates that activated Ras enhances the ability of C/EBPa to transactivate the G-CSF receptor promoter and a minimal promoter containing only C/EBP DNA binding sites. Ras signaling activates C/EBPa via the transactivation domain, because it enhances the transactivation function of a fusion protein containing a Gal4 DNA binding domain and the C/EBPa transactivation domain, and does not change C/EBPa DNA binding. Ras acts on serine 248 of the C/EBPa transactivation domain, as it does not enhance the transactivation function of a C/EBPa serine 248 to alanine point mutant. Interestingly, serine 248 of C/EBPa is a PKC consensus site, and a PKC inhibitor blocks the activation of C/EBPa by Ras. Ras signaling phosphorylates C/EBPa on serine 248 in vivo. Finally, mutation of serine 248 to alanine obviates the ability of C/EBPa to induce granulocytic differentiation. These data suggest a model where Ras signaling enhances the activity of C/EBPa to induce granulocytic differentiation by phosphorylation of serine 248.","abstract_html":"The transcription factor C/EBPa regulates early steps of normal granulocyte differentiation since mice with a disruption of the C/EBPa gene do not express detectable levels of the G-CSF receptor and produce no neutrophils. We have recently shown that C/EBPa function is also impaired in acute myeloid leukemias. However, how the transcriptional activity of C/EBPa is regulated both in myelopoiesis and leukemogenesis, is not fully understood. The current study demonstrates that activated Ras enhances the ability of C/EBPa to transactivate the G-CSF receptor promoter and a minimal promoter containing only C/EBP DNA binding sites. Ras signaling activates C/EBPa via the transactivation domain, because it enhances the transactivation function of a fusion protein containing a Gal4 DNA binding domain and the C/EBPa transactivation domain, and does not change C/EBPa DNA binding. Ras acts on serine 248 of the C/EBPa transactivation domain, as it does not enhance the transactivation function of a C/EBPa serine 248 to alanine point mutant. Interestingly, serine 248 of C/EBPa is a PKC consensus site, and a PKC inhibitor blocks the activation of C/EBPa by Ras. Ras signaling phosphorylates C/EBPa on serine 248 in vivo. Finally, mutation of serine 248 to alanine obviates the ability of C/EBPa to induce granulocytic differentiation. These data suggest a model where Ras signaling enhances the activity of C/EBPa to induce granulocytic differentiation by phosphorylation of serine 248.","abstract_has_math":false,"creators":["Singh, Sheo Mohan"],"institution":"Ludwig-Maximilians-Universität","degree_name":null,"degree_level":"thesis.doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2003,"date_issued":"2003-07-22","date_published":"2003-07-22","updated_at":"2026-07-24T02:51:44Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://edoc.ub.uni-muenchen.de/1235/","outbound_label":"Repository record","outbound_source":"source_url"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Singh, Sheo Mohan"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:publisher","label":"Institution","values":["Universitätsbibliothek der Ludwig-Maximilians-Universität"]},{"key":"dc:type","label":"Dc Type","values":["doctoralThesis"]},{"key":"thesis:degree_level","label":"Degree Level","values":["thesis.doctoral"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Ludwig-Maximilians-Universität"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The transcription factor C/EBPa regulates early steps of normal granulocyte differentiation since mice with a disruption of the C/EBPa gene do not express detectable levels of the G-CSF receptor and produce no neutrophils. We have recently shown that C/EBPa function is also impaired in acute myeloid leukemias. However, how the transcriptional activity of C/EBPa is regulated both in myelopoiesis and leukemogenesis, is not fully understood. The current study demonstrates that activated Ras enhances the ability of C/EBPa to transactivate the G-CSF receptor promoter and a minimal promoter containing only C/EBP DNA binding sites. Ras signaling activates C/EBPa via the transactivation domain, because it enhances the transactivation function of a fusion protein containing a Gal4 DNA binding domain and the C/EBPa transactivation domain, and does not change C/EBPa DNA binding. Ras acts on serine 248 of the C/EBPa transactivation domain, as it does not enhance the transactivation function of a C/EBPa serine 248 to alanine point mutant. Interestingly, serine 248 of C/EBPa is a PKC consensus site, and a PKC inhibitor blocks the activation of C/EBPa by Ras. Ras signaling phosphorylates C/EBPa on serine 248 in vivo. Finally, mutation of serine 248 to alanine obviates the ability of C/EBPa to induce granulocytic differentiation. These data suggest a model where Ras signaling enhances the activity of C/EBPa to induce granulocytic differentiation by phosphorylation of serine 248."]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Ras signaling enhances the activity of C/EBPalpha to induce granulocytic differentiation by phosphorylation of serine 248"]}]}],"canonical_facts":{"dc:creator":["Singh, Sheo Mohan"],"dc:description.abstract":["The transcription factor C/EBPa regulates early steps of normal granulocyte differentiation since mice with a disruption of the C/EBPa gene do not express detectable levels of the G-CSF receptor and produce no neutrophils. We have recently shown that C/EBPa function is also impaired in acute myeloid leukemias. However, how the transcriptional activity of C/EBPa is regulated both in myelopoiesis and leukemogenesis, is not fully understood. The current study demonstrates that activated Ras enhances the ability of C/EBPa to transactivate the G-CSF receptor promoter and a minimal promoter containing only C/EBP DNA binding sites. Ras signaling activates C/EBPa via the transactivation domain, because it enhances the transactivation function of a fusion protein containing a Gal4 DNA binding domain and the C/EBPa transactivation domain, and does not change C/EBPa DNA binding. Ras acts on serine 248 of the C/EBPa transactivation domain, as it does not enhance the transactivation function of a C/EBPa serine 248 to alanine point mutant. Interestingly, serine 248 of C/EBPa is a PKC consensus site, and a PKC inhibitor blocks the activation of C/EBPa by Ras. Ras signaling phosphorylates C/EBPa on serine 248 in vivo. Finally, mutation of serine 248 to alanine obviates the ability of C/EBPa to induce granulocytic differentiation. These data suggest a model where Ras signaling enhances the activity of C/EBPa to induce granulocytic differentiation by phosphorylation of serine 248."],"dc:format.medium":["application/pdf"],"dc:publisher":["Universitätsbibliothek der Ludwig-Maximilians-Universität"],"dc:title":["Ras signaling enhances the activity of C/EBPalpha to induce granulocytic differentiation by phosphorylation of serine 248"],"dc:type":["doctoralThesis"],"thesis:degree_level":["thesis.doctoral"],"thesis:institution_name":["Ludwig-Maximilians-Universität"]},"updated_at":"2026-07-24T02:51:44Z"}