The effects of two different potent inhibitors of protein kinase C, 1- (5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) and staurosporine on human myeloid (CFU-C) and late erythroid progenitor cells (CFU-E) were studied using an in vitro clonal assay. Our objective was to determine whether protein kinase C has a role in signal transduction related to proliferation of these committed progenitor cells. The presence of H-7 or staurosporine led to an inhibition of colony formation stimulated by crude colony-stimulating factor (CSF), interleukin-3 (IL-3), granulocyte-macrophage CSF (GM-CSF), granulocyte CSF (G-CSF), or macrophage CSF (M-CSF) in a dose-dependent manner. N-(2-guanidinoethyl)- 5-isoquinolinesulfonamide (HA-1004), a weaker analog of H-7, did not inhibit proliferation of CFU-C. Neither H-7 nor staurosporine had any effect on CFU-E formation. H-7 and staurosporine dose-dependently inhibited the protein kinase C from K562 cells. The potential of these compounds to inhibit proliferation of CFU-C correlated well with the magnitude of their inhibition of protein kinase C from K562 cells. The inhibition of proliferation of CFU-C appears to relate to the potential of these compounds to inhibit protein kinase C. Thus, activation of protein kinase C is presumably involved in the proliferation of CFU-C, and the regulatory system of CFU-E appears to differ from that of CFU-C.
Putative involvement of protein kinase C in proliferation of human myeloid progenitor cells
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N Katayama, M Nishikawa, N Minami, S Shirakawa; Putative involvement of protein kinase C in proliferation of human myeloid progenitor cells. Blood 1989; 73 (1): 123–130. doi: https://doi.org/10.1182/blood.V73.1.123.bloodjournal731123
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