Defective G-CSFR signaling pathways in congenital neutropenia.
Several signaling systems downstream of G-CSFR have been identified that are defective or hyperactivated in myeloid cells of patients with congenital neutropenia: severely reduced expression of myeloid-specific transcription factors LEF-1 and C/EBPα, severely reduced expression and functions of HCLS1 protein, severely reduced expression of neutrophil elastase protein, dramatic compensatory up-regulation of the NAMPT/NAD(+)/SIRT pathway leading to continuous activation of emergency granulopoiesis via the transcription factor C/EBPβ, and hyperactivation of STAT5 protein by tyrosine phosphorylation.
Department of Molecular Hematopoiesis, Children's Hospital, Hannover Medical School, Carl-Neuberg Strasse 1, Hannover 30625, Germany. skokowa.julia@mh-hannover.de
Julia
J
Skokowa
Karl
K
Welte
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D001798:Blood Proteins / Q000235:genetics; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D019272:Leukocyte Elastase / Q000235:genetics; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics; D009154:Mutation; D022423:Myeloid Cells / Q000378:metabolism; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000378:metabolism; D038042:Myelopoiesis / Q000235:genetics; D009503:Neutropenia / Q000151:congenital* / Q000235:genetics* / Q000378:metabolism; D054409:Nicotinamide Phosphoribosyltransferase / Q000378:metabolism; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics*; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D001798:Blood Proteins; D022763:CCAAT-Enhancer-Binding Protein-alpha; C104759:HAX1 protein, human; C061909:HCLS1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D054409:Nicotinamide Phosphoribosyltransferase; D019272:Leukocyte Elastase