title: G-CSF receptor mutations in patients with severe congenital neutropenia do not abrogate Jak2 activation and stat1/stat3 translocation.
abstract: Severe congenital neutropenia (SCN) is an inherited disorder of myelopoiesis, characterized by a maturation arrest at the stage of promyelocytes and myelocytes in bone marrow, and absence or low levels of mature neutrophil granulocytes in peripheral blood. Recently, studies of patients with SCN who subsequently developed acute myeloid leukemia (AML) revealed nonsense mutations in the cytoplasmic domain of the granulocyte colony-stimulating factor (G-CSF) receptor messenger RNA. We focused our interest on the G-CSF-mediated signaling cascade to examine the consequences of the observed point mutations for the nuclear translocation of the transcription factors Stat1 and Stat3. Expression vectors encoding for truncated G-CSF receptors were transfected in the murine fibroblast cell line C243 expressing a fusion protein consisting of the transcription factor Stat1 and Stat3, respectively, and the green fluorescent protein (GFP). Nuclear translocation of the GFP fusion proteins was examined after G-CSF stimulation of the transfected cells.
authors.affiliation: Department of Pediatric Hematology and Oncology, Hannover Medical School, Germany. Welte.Karl@MH-Hannover.de
authors.forename: A
authors.initials: A
authors.lastname: Herbst
authors.forename: M
authors.initials: M
authors.lastname: Koester
authors.forename: D
authors.initials: D
authors.lastname: Wirth
authors.forename: H
authors.initials: H
authors.lastname: Hauser
authors.forename: K
authors.initials: K
authors.lastname: Welte
mesh_terms: D001853:Bone Marrow / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D053614:Janus Kinase 2; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D008954:Models, Biological; D020125:Mutation, Missense; D009503:Neutropenia / Q000151:congenital / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000235:genetics; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics*; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2