Phorbol ester-induced alteration of differentiation and proliferation in human hematopoietic tumor cell lines: relationship to the presence and subcellular distribution of protein kinase C.
The intracellular translocation of protein kinase C (PKC) from the soluble to the membranous fraction has been shown previously to correlate with biological activity of phorbol esters in several systems. In this paper, we describe that PKC translocation was a general phenomenon in all PKC containing cell types when five 12-O-tetradecanoylphorbol-13-acetate (TPA) responsive and nonresponsive hematopoietic tumor cell lines were investigated. The nonresponsive cell line U-266 contained undetectable levels of PKC. The dose of TPA required for translocation was similar to the TPA concentration necessary to suppress erythroid differentiation in K-562 cells and to induce macrophage differentiation in U-937 cells, but 100-fold higher than that required for suppression of proliferation in K-562 and U-937 cells. By contrast, PKC translocation and TPA induced proliferation inhibition exhibited a similar dose dependence in a subline of U-937 (U-937 RES) adapted to growth in the presence of 10(-9) M TPA. It is suggested that U-937 RES is deficient in a TPA dependent but PKC independent signal pathway.
D001692:Biological Transport / Q000187:drug effects; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D002451:Cell Compartmentation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004920:Erythropoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D010704:Phorbols / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D011955:Receptors, Drug; D011971:Receptors, Immunologic / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D010704:Phorbols; D011955:Receptors, Drug; D011971:Receptors, Immunologic; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate