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dc.contributor.authorWhetton, Anthony Den
dc.contributor.authorHeyworth, Clare Men
dc.contributor.authorNicholls, S Een
dc.contributor.authorEvans, C Aen
dc.contributor.authorLord, J Men
dc.contributor.authorDexter, T Michaelen
dc.contributor.authorOwen-Lynch, P Jen
dc.date.accessioned2010-04-09T13:56:25Z
dc.date.available2010-04-09T13:56:25Z
dc.date.issued1994-05
dc.identifier.citationCytokine-mediated protein kinase C activation is a signal for lineage determination in bipotential granulocyte macrophage colony-forming cells. 1994, 125 (3):651-9 J. Cell Biol.en
dc.identifier.issn0021-9525
dc.identifier.pmid7513707
dc.identifier.urihttp://hdl.handle.net/10541/96190
dc.description.abstractGranulocyte macrophage colony-forming cells (GM-CFC) have the potential to develop into either macrophages and/or neutrophils. With a highly enriched population of these cells we have found that although GM-CFC are equally responsive to macrophage colony stimulating factor (M-CSF) and stem cell factor (SCF) in terms of DNA synthesis, M-CSF stimulated the development of colonies containing macrophages in soft gel assays, while SCF promoted neutrophilic colony formation. When SCF and M-CSF were combined, mainly macrophage development was stimulated both in soft agar colony-forming assays and liquid cultures. An analysis of some potential signaling mechanisms associated with cytokine-mediated developmental decisions in GM-CFC revealed that M-CSF, but not SCF, was able to chronically stimulate phosphatidylcholine breakdown and diacylglycerol production, indicating that protein kinase C (PKC) may be involved in the action of M-CSF. Furthermore, M-CSF, but not SCF, can increase the levels of PKC alpha (PKC alpha) expression and stimulate the translocation of PKC alpha to the nucleus. When the PKC inhibitor, calphostin C, was added to GM-CFC cultured in M-CSF then predominantly neutrophils were produced, conversely PKC activators added with SCF stimulated macrophage development. The data indicate a role for PKC in M-CSF-stimulated macrophage development from GM-CFC.
dc.language.isoenen
dc.subjectHaematopoiesisen
dc.subjectHaematopoietic Cell Growth Factorsen
dc.subjectHaematopoietic Stem Cellsen
dc.subject.meshAnimals
dc.subject.meshBone Marrow Cells
dc.subject.meshCell Differentiation
dc.subject.meshCell Division
dc.subject.meshCell Separation
dc.subject.meshCells, Cultured
dc.subject.meshDiglycerides
dc.subject.meshEnzyme Activation
dc.subject.meshHematopoiesis
dc.subject.meshHematopoietic Cell Growth Factors
dc.subject.meshHematopoietic Stem Cells
dc.subject.meshInositol Phosphates
dc.subject.meshMacrophage Colony-Stimulating Factor
dc.subject.meshMacrophages
dc.subject.meshMice
dc.subject.meshNeutrophils
dc.subject.meshProtein Kinase C
dc.subject.meshSecond Messenger Systems
dc.subject.meshStem Cell Factor
dc.titleCytokine-mediated protein kinase C activation is a signal for lineage determination in bipotential granulocyte macrophage colony-forming cells.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biochemistry and Applied Molecular Biology, UMIST, Manchester, United Kingdom.en
dc.identifier.journalThe Journal of Cell Biologyen
html.description.abstractGranulocyte macrophage colony-forming cells (GM-CFC) have the potential to develop into either macrophages and/or neutrophils. With a highly enriched population of these cells we have found that although GM-CFC are equally responsive to macrophage colony stimulating factor (M-CSF) and stem cell factor (SCF) in terms of DNA synthesis, M-CSF stimulated the development of colonies containing macrophages in soft gel assays, while SCF promoted neutrophilic colony formation. When SCF and M-CSF were combined, mainly macrophage development was stimulated both in soft agar colony-forming assays and liquid cultures. An analysis of some potential signaling mechanisms associated with cytokine-mediated developmental decisions in GM-CFC revealed that M-CSF, but not SCF, was able to chronically stimulate phosphatidylcholine breakdown and diacylglycerol production, indicating that protein kinase C (PKC) may be involved in the action of M-CSF. Furthermore, M-CSF, but not SCF, can increase the levels of PKC alpha (PKC alpha) expression and stimulate the translocation of PKC alpha to the nucleus. When the PKC inhibitor, calphostin C, was added to GM-CFC cultured in M-CSF then predominantly neutrophils were produced, conversely PKC activators added with SCF stimulated macrophage development. The data indicate a role for PKC in M-CSF-stimulated macrophage development from GM-CFC.


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