M-CSF induced differentiation of myeloid precursor cells involves activation of PKC-delta and expression of Pkare.
Macrophage-colony stimulating factor (M-CSF) regulates proliferation and differentiation of cells belonging to the monocytic lineage. We investigated the mechanisms of M-CSF differentiation signaling in follicular dendritic cell-P1 cells and analyzed the catalytic activation of different protein kinase C (PKC) isoforms. M-CSF induced rapid catalytic activation of PKC-delta and membrane translocation of the tyrosine phosphorylated form of PKC-delta. Mutation of tyrosine 807 in the M-CSF receptor (Fms) abrogates cell differentiation but not a proliferative response to M-CSF, and FmsY807F failed to activate PKC-delta. We also investigated the downstream signaling pathways from PKC-delta. A cyclic adenosine monophosphate-regulated Ser/Thr kinase gene, protein kinase X (PRKX), has been associated with macrophage differentiation in human cells. We found that M-CSF and PKC-delta induced the expression of the PRKX murine homologue: PKA-related gene. Taken together, our results indicate that PKC-delta functions as a critical mediator of M-CSF-induced differentiation signaling.
Junttila
Ilkka
I
Laboratory of Molecular Immunology, Institute of Medical Technology, Tampere University Hospital, University of Tampere, Lenkkeilijänkatu 8, 33014 Tampere, Finland.
Bourette
Roland P
RP
Rohrschneider
Larry R
LR
Silvennoinen
Olli
O
D000581:Amidohydrolases; D000626:Aminopeptidases / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D007527:Isoenzymes / Q000502:physiology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology*; D051745:Protein Kinase C-delta; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D021381:Protein Transport; D014443:Tyrosine / Q000378:metabolism
D007527:Isoenzymes; D014443:Tyrosine; D016173:Macrophage Colony-Stimulating Factor; C109450:PRKX protein, human; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D000626:Aminopeptidases; D000581:Amidohydrolases; C084507:peptide deformylase