Protein kinase C in erythroid and megakaryocytic differentiation: possible role in lineage determination.
Erythroid differentiation of normal human hematopoietic progenitor cells was drastically inhibited by phorbol ester, 12-myristate 13-acetate (PMA), an agent known to activate the class of serine-threonine kinases, protein kinase C (PKC). This inhibition was accompanied by augmented megakaryocytic differentiation as demonstrated by expression of megakaryocyte-specific mRNAs and proteins. These effects of PMA were reversed by two specific antagonists of PKC. Analysis of single colonies transferred from cultures not containing PMA to PMA-containing cultures indicated that, in this system, PMA exerts megakaryocytic differentiating activity directly on cells which may have already initiated a progression toward the erythroid pathway of differentiation. These results suggest that modulation of PKC activity plays a role in erythroid and megakaryocytic differentiation, and may constitute an important selective signal between these pathways during normal blood cell development.
Lumelsky
N L
NL
William Middleton Veteran Affairs Hospital and Department of Medicine, University of Wisconsin, Madison 53706, USA. lumelsky@facstaff.wisc.edu
Schwartz
B S
BS
D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004912:Erythrocytes / Q000201:enzymology*; D005434:Flow Cytometry; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D008533:Megakaryocytes / Q000201:enzymology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate