epidermal-growth-factor and phorbol-12-13-dibenzoate

The level of occupancy of a single class of high-affinity (3H)-phorbol 12, 13-dibutyrate (PDBu) binding sites (Kd = 26 nM) in quiescent Swiss 3T3 cells was correlated with the dose of PDBu required to stimulate rapid (increase in 86Rb uptake, decrease in epidermal growth factor receptor affinity) and long-term (induction of 2-deoxyglucose uptake, initiation of DNA synthesis) events of the proliferative response. Further, structural analogues of PDBu showed identical relative potencies in the inhibition of (3H)-PDBu binding and stimulation of DNA synthesis. Finally, prolonged (24-hour) incubation of Swiss 3T3 or whole mouse embryo fibroblasts with 400 nM PDBu led to a decrease in the number of (3H)-PDBu binding sites (down-regulation) with a parallel loss of rapid and long-term responses of the cells to PDBu (desensitization). These findings indicate that the high-affinity (3H)-PDBu binding sites mediate the mitogenic effects of phorbol esters in fibroblastic cells.

Topics: Animals; Biological Transport, Active; Caenorhabditis elegans Proteins; Carcinogens; Carrier Proteins; Cells, Cultured; Deoxyglucose; DNA Replication; Epidermal Growth Factor; ErbB Receptors; Fibroblasts; Kinetics; Mice; Mitogens; Phorbol Esters; Phorbols; Protein Kinase C; Receptors, Cell Surface; Receptors, Drug