Specific receptors for phorbol esters in lymphoid cell populations: role in enhanced production of T-cell growth factor.
Phorbol ester tumor promoters act synergistically with concanavalin A to cause production of T-cell growth factor by normal human peripheral blood lymphocytes. A specific, saturable, binding component which may mediate the phorbol ester effect has been identified by using [20-3H]phorbol 12,13-dibutyrate in a whole-cell binding assay. Specific binding is maximal with 5 min at 37 or 23 degrees C but the level of bound ligand rapidly decreases to about 50% within 1 hr. At 4 degrees C, 2 hr are required to reach maximal binding, and the binding is stable for at least 20 hr. Binding is reversible at 37 and 4 degrees C with time courses similar to those for initial binding at the respective temperatures. Saturation of the specific binding occurs at a concentration (approximately 30 nM) consistent with that producing maximal T-cell growth factor activity. Scatchard analysis of the binding after 30 min at 37 degrees C demonstrates a lower Kd (9 nM) than that determined after 2 hr at 4 degrees C (22 nM). The median number of sites per cell for six donors was 2 X 10(5) (range, 1.3-4 X 10(5). Other tumor-promoting phorbol esters compete for [20-3H]phorbol 12,13-dibutyrate binding in approximate proportion to their activity in stimulating T-cell growth factor production. Phorbol, 4-alpha-phorbol didecanoate, dexamethasone, retinoic acid, butyric acid, and dimethyl sulfoxide do not compete for specific binding.
D029742:Caenorhabditis elegans Proteins; D002273:Carcinogens / Q000378:metabolism; D002352:Carrier Proteins; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D007700:Kinetics; D008222:Lymphokines / Q000096:biosynthesis*; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000097:blood*; D010704:Phorbols / Q000097:blood*; D011493:Protein Kinase C; D011955:Receptors, Drug / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000097:blood
D029742:Caenorhabditis elegans Proteins; D002273:Carcinogens; D002352:Carrier Proteins; D007376:Interleukin-2; D008222:Lymphokines; D010703:Phorbol Esters; D010704:Phorbols; D011955:Receptors, Drug; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate