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J. Cell Biol., Volume 140, Number 6, March 23, 1998 1511-1518

An Activated Protein Kinase C alpha  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,Dagger T. Michael Dexter,§ Janet M. Lord,par P. Jane Owen-Lynch,* Gwen Wark,* and Anthony D. Whetton*

* Leukaemia Research Fund Cellular Development Unit, Dagger  Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, Manchester, M60 1QD, United Kingdom; § Cancer Research Campaign, Department of Experimental Hematology, Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Manchester, M20 9BX, United Kingdom; and par  Department of Immunology, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom

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.


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