title: Endogenous K-ras signaling in erythroid differentiation.
abstract: K-ras is one of the most frequently mutated genes in virtually all types of human cancers. Using mouse fetal liver erythroid progenitors as a model system, we studied the role of endogenous K-ras signaling in erythroid differentiation. When oncogenic K-ras is expressed from its endogenous promoter, it hyperactivates cytokine-dependent signaling pathways and results in a partial block in erythroid differentiation. In erythroid progenitors deficient in K-ras, cytokine-dependent Akt activation is greatly reduced, leading to delays in erythroid differentiation. Thus, both loss- and gain-of-Kras functions affect erythroid differentiation through modulation of cytokine signaling. These results support the notion that in human cancer patients oncogenic Ras signaling might be controlled by antagonizing essential cytokines.
authors.affiliation: Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Harvey F
authors.initials: HF
authors.lastname: Lodish
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism*; D004921:Erythropoietin / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008954:Models, Biological; D009154:Mutation; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D004921:Erythropoietin; D018631:ras Proteins