An activated protein kinase C alpha gives a differentiation signal for hematopoietic progenitor cells and mimicks macrophage colony-stimulating factor-stimulated signaling events.

2.50
Hdl Handle:
http://hdl.handle.net/10541/92761
Title:
An activated protein kinase C alpha gives a differentiation signal for hematopoietic progenitor cells and mimicks macrophage colony-stimulating factor-stimulated signaling events.
Authors:
Pierce, A; Heyworth, Clare M; Nicholls, S E; Spooncer, Elaine; Dexter, T Michael; Lord, J M; Owen-Lynch, P J; Wark, G; Whetton, Anthony D
Abstract:
Highly enriched, bipotent, hematopoietic granulocyte macrophage colony-forming cells (GM-CFC) require cytokines for their survival, proliferation, and development. GM-CFC will form neutrophils in the presence of the cytokines stem cell factor and granulocyte colony-stimulating factor, whereas macrophage colony-stimulating factor leads to macrophage formation. Previously, we have shown that the commitment to the macrophage lineage is associated with lipid hydrolysis and translocation of protein kinase C alpha (PKCalpha) to the nucleus. Here we have transfected freshly prepared GM-CFC with a constitutively activated form of PKCalpha, namely PKAC, in which the regulatory domain has been truncated. Greater than 95% of the transfected cells showed over a twofold increase in PKCalpha expression with the protein being located primarily within the nucleus. The expression of PKAC caused macrophage development even in the presence of stimuli that normally promote only neutrophilic development. Thus, M-CSF-stimulated translocation of PKCalpha to the nucleus is a signal associated with macrophage development in primary mammalian hematopoietic progenitor cells, and this signal can be mimicked by ectopic PKAC, which is also expressed in the nucleus.
Affiliation:
Leukaemia Research Fund Cellular Development Unit, University of Manchester Institute of Science and Technology, Manchester, M60 1QD, United Kingdom.
Citation:
An activated protein kinase C alpha gives a differentiation signal for hematopoietic progenitor cells and mimicks macrophage colony-stimulating factor-stimulated signaling events. 1998, 140 (6):1511-8 J. Cell Biol.
Journal:
The Journal of Cell Biology
Issue Date:
23-Mar-1998
URI:
http://hdl.handle.net/10541/92761
PubMed ID:
9508782
Type:
Article
Language:
en
ISSN:
0021-9525
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorPierce, Aen
dc.contributor.authorHeyworth, Clare Men
dc.contributor.authorNicholls, S Een
dc.contributor.authorSpooncer, Elaineen
dc.contributor.authorDexter, T Michaelen
dc.contributor.authorLord, J Men
dc.contributor.authorOwen-Lynch, P Jen
dc.contributor.authorWark, Gen
dc.contributor.authorWhetton, Anthony Den
dc.date.accessioned2010-02-23T13:24:17Z-
dc.date.available2010-02-23T13:24:17Z-
dc.date.issued1998-03-23-
dc.identifier.citationAn activated protein kinase C alpha gives a differentiation signal for hematopoietic progenitor cells and mimicks macrophage colony-stimulating factor-stimulated signaling events. 1998, 140 (6):1511-8 J. Cell Biol.en
dc.identifier.issn0021-9525-
dc.identifier.pmid9508782-
dc.identifier.urihttp://hdl.handle.net/10541/92761-
dc.description.abstractHighly enriched, bipotent, hematopoietic granulocyte macrophage colony-forming cells (GM-CFC) require cytokines for their survival, proliferation, and development. GM-CFC will form neutrophils in the presence of the cytokines stem cell factor and granulocyte colony-stimulating factor, whereas macrophage colony-stimulating factor leads to macrophage formation. Previously, we have shown that the commitment to the macrophage lineage is associated with lipid hydrolysis and translocation of protein kinase C alpha (PKCalpha) to the nucleus. Here we have transfected freshly prepared GM-CFC with a constitutively activated form of PKCalpha, namely PKAC, in which the regulatory domain has been truncated. Greater than 95% of the transfected cells showed over a twofold increase in PKCalpha expression with the protein being located primarily within the nucleus. The expression of PKAC caused macrophage development even in the presence of stimuli that normally promote only neutrophilic development. Thus, M-CSF-stimulated translocation of PKCalpha to the nucleus is a signal associated with macrophage development in primary mammalian hematopoietic progenitor cells, and this signal can be mimicked by ectopic PKAC, which is also expressed in the nucleus.en
dc.language.isoenen
dc.subjectHaematopoietic Stem Cellsen
dc.subject.meshAnimals-
dc.subject.meshCulture Media-
dc.subject.meshEnzyme Activation-
dc.subject.meshFlow Cytometry-
dc.subject.meshGranulocyte-Macrophage Colony-Stimulating Factor-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshInterleukin-3-
dc.subject.meshIsoenzymes-
dc.subject.meshMice-
dc.subject.meshMicroscopy, Confocal-
dc.subject.meshProtein Kinase C-
dc.subject.meshProtein Kinase C-alpha-
dc.subject.meshSignal Transduction-
dc.subject.meshTransfection-
dc.titleAn activated protein kinase C alpha gives a differentiation signal for hematopoietic progenitor cells and mimicks macrophage colony-stimulating factor-stimulated signaling events.en
dc.typeArticleen
dc.contributor.departmentLeukaemia Research Fund Cellular Development Unit, University of Manchester Institute of Science and Technology, Manchester, M60 1QD, United Kingdom.en
dc.identifier.journalThe Journal of Cell Biologyen
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