Partial purification and characterization of a binding protein for biologically active phorbol and ingenol esters from murine sera.
We have purified a protein (Mr approximately 71,000) from murine sera 104-fold which directly binds biologically active phorbol esters, ingenol esters, and mezerein in a specific, reversible, and saturable manner. The binding of labeled phorbol-12,13-dibutyrate (PDBu) to the purified protein is rapid and dose-dependent. Those phorbol and ingenol esters which stimulate cell growth in culture and have tumor-promoting activity in vivo inhibit the binding of labeled PDBu, while the biologically inactive derivatives fail to do so. Other nonditerpene tumor promoters, retinoids, steroids, and prostaglandins do not interfere with PDBu-protein interaction. Epidermal growth factor, insulin, bovine serum albumin, hemoglobin, ovalbumin, ferritin, myoglobin, fetuin, and lipase do not interact directly with PDBu. The purified binding protein competitively inhibits the binding of PDBu to its specific receptors. It is nonglycosylated and slightly hydrophobic. The protein is heat- and acid-labile and is present in sera of various mammalian species. Its concentration in murine sera is age-, sex-, and strain-independent.
D000818:Animals; D001921:Brain / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins; D002273:Carcinogens / Q000378:metabolism; D002352:Carrier Proteins; D002462:Cell Membrane / Q000378:metabolism; D004224:Diterpenes / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D051379:Mice; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000378:metabolism*; D010704:Phorbols / Q000378:metabolism*; D011493:Protein Kinase C; D011955:Receptors, Drug / Q000302:isolation & purification / Q000378:metabolism*; D013045:Species Specificity
D029742:Caenorhabditis elegans Proteins; D002273:Carcinogens; D002352:Carrier Proteins; D004224:Diterpenes; D010703:Phorbol Esters; D010704:Phorbols; D011955:Receptors, Drug; C027777:ingenol ester receptor; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C