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

Andrew Pierce, Clare M. Heyworth, Sian E. Nicholls, Elaine Spooncer, T. Michael Dexter, Janet M. Lord, P. Jane Owen-Lynch, Gwen Wark, Anthony D. Whetton

Research output: Contribution to journalArticle

39 Citations (Scopus)

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 α (PKCα) to the nucleus. Here we have transfected freshly prepared GM-CFC with a constitutively activated form of PKCα, namely PKAC, in which the regulatory domain has been truncated. Greater than 95% of the transfected cells showed over a twofold increase in PKCα 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 PKCα 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.

Original languageEnglish
Pages (from-to)1511-1518
Number of pages8
JournalJournal of Cell Biology
Volume140
Issue number6
DOIs
Publication statusPublished - 23 Mar 1998
Externally publishedYes

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Macrophage Colony-Stimulating Factor
Hematopoietic Stem Cells
Protein Kinase C
Macrophages
Granulocytes
Cytokines
Stem Cell Factor
Granulocyte Colony-Stimulating Factor
Neutrophils
Hydrolysis
Lipids

Cite this

Pierce, Andrew ; Heyworth, Clare M. ; Nicholls, Sian E. ; Spooncer, Elaine ; Dexter, T. Michael ; Lord, Janet M. ; Owen-Lynch, P. Jane ; Wark, Gwen ; Whetton, Anthony D. / An activated protein kinase C α gives a differentiation signal for hematopoietic progenitor cells and mimicks macrophage colony-stimulating factor-stimulated signaling events. In: Journal of Cell Biology. 1998 ; Vol. 140, No. 6. pp. 1511-1518.
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An activated protein kinase C α gives a differentiation signal for hematopoietic progenitor cells and mimicks macrophage colony-stimulating factor-stimulated signaling events. / Pierce, Andrew; Heyworth, Clare M.; Nicholls, Sian E.; Spooncer, Elaine; Dexter, T. Michael; Lord, Janet M.; Owen-Lynch, P. Jane; Wark, Gwen; Whetton, Anthony D.

In: Journal of Cell Biology, Vol. 140, No. 6, 23.03.1998, p. 1511-1518.

Research output: Contribution to journalArticle

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AU - Pierce, Andrew

AU - Heyworth, Clare M.

AU - Nicholls, Sian E.

AU - Spooncer, Elaine

AU - Dexter, T. Michael

AU - Lord, Janet M.

AU - Owen-Lynch, P. Jane

AU - Wark, Gwen

AU - Whetton, Anthony D.

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AB - 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 α (PKCα) to the nucleus. Here we have transfected freshly prepared GM-CFC with a constitutively activated form of PKCα, namely PKAC, in which the regulatory domain has been truncated. Greater than 95% of the transfected cells showed over a twofold increase in PKCα 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 PKCα 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.

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