TPA induces subcellular translocation and subsequent down-regulation of both phorbol ester binding and protein kinase C activities in MCF-7 cells.
Phorbol ester TPA has been previously shown to induce a rapid translocation, followed by a progressive decline of protein kinase C activity in MCF-7 cells (J.M. Darbon et al, 1986, Biochem. Biophys. Res. Comm. 137: 1159-1166). We show now a parallel TPA-induced movement of phorbol ester binding sites from the cytosolic to the particulate fraction with no change in the binding affinities for the (3H) PDBu probe (KD congruent to 2 nM). The subcellular redistribution process is followed by a rapid decrease of the phorbol ester binding capacity at the membrane level. The concomitant decline in both phorbol ester binding and protein kinase C activities that we observed during the course of TPA treatment strongly argues for a real down-regulation of the enzyme in phorbol ester-treated MCF-7 cells. The molecular mechanisms of these events and their relations to the inhibition of cell growth remain to be clarified.
D000818:Animals; D001665:Binding Sites; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D002460:Cell Line; D007700:Kinetics; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011955:Receptors, Drug; D011971:Receptors, Immunologic / Q000378:metabolism*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D010703:Phorbol Esters; D011955:Receptors, Drug; D011971:Receptors, Immunologic; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate