The site of action of the phorbol esters, potent tumor promoters, is not known. To evaluate the possible role of the nucleus in the specific interaction of phorbol esters with cells, the activity of phorbol-12-myristate-13-acetate was determined on intact and enucleated Swiss 3T3 mouse cells. The parameter which was used as a measure of cellular response was the morphological change of transien...

PRAS40 binds to the mTORC1 (mammalian target of rapamycin complex 1) and is released in response to insulin. It has been suggested that this effect is due to 14-3-3 binding and leads to activation of mTORC1 signalling. In a similar manner to insulin, phorbol esters also activate mTORC1 signalling, in this case via PKC (protein kinase C) and ERK (extracellular-signal-regulated kinase). However, ...

The human promyelocytic leukemia cell line HL-60 can be induced to differentiate into macrophage-like cells by nanomolar concentrations of phorbol esters. A phorbol ester-resistant var iant R1B6 obtained by culturing HL-60 cells with increasing concentrations of 12-O-tetradecanoylphorbol-13-acetate, is reversibly resistant. These cells have been growing continuously in the presence of phorbol e...

We examined the ability of a series of highly lipophilic phorbol esters to inhibit [20-3H]phorbol 12,13-dibutyrate binding to the cytosolic aporeceptor from mouse brain. If added in the usual fashion directly into the aqueous phase of the assay mixture, phorbol 12,13-distearate, phorbol 12,13-dioleate, and phorbol 12,13-dimyristate showed very weak inhibitory activities, with apparent inhibitor...

DNA-histone interaction resulting in increased gene activation (1 , 13). In an effort to observe any existing correlation between the phosphorylation of mouse epidermal histones, tumor promotion, and the increased epidermal macro molecular biosynthesis caused by phorbol esters, we have studied the effect and specificity of some phorbol esters on histone phosphorylation, both in the intact mouse...

A. Marston and E. Hecker***** Institut für Biochemie, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-6900 Heidelberg, FRG Z. Naturforsch. 38b, 1015-1021 (1983); received March 28, 1983 Amino Acids, Peptides, Phorbol Esters, Irritants, Tumour Promoters The synthesis of a series of 12-O-amino acyland 12-0-peptidyl-13-acetate and -13,20diacetate esters of the tetracyclic diterpene al...

Phorbol esters induce drastic morphological alterations in cells of different origin by altering the conformation and the interrelationship of the elements of the cytoskeletal system. Treatment of early passage (young) and late passage (senescent) human fibroblasts MRC-5 with phorbol-12-myristate-13-acetate (PMA) results in the rearrangement of actin and tubulin filaments. PMA brings about the ...

We have investigated the effect of phorbol dibutyrate on intracellular routing of the asialoglycoprotein receptor (ASGP-R) in a human hepatoma cell line, Hep G2. We have previously shown that this agent causes a net redistribution of 50% of cell surface receptors to the cell interior (Fallon, R.J., and A.L. Schwartz, J. Biol. Chem. 261: 15081-15089 (1986)). To explore the mechanism of this effe...

Aggregation of marine sponge cells (Microciona prolifera) resembles stimulus-response coupling of higher organisms in which activation of protein kinase C and movements of intracellular Ca provide twin signals. We now report that activators of protein kinase C (phorbol esters) and ionomycin act synergistically to aggregate sponge cells. Surprisingly--since extracellular Ca is required for integ...

The bryostatins, macrocyclic lactones isolated on the basis of their antineoplastic activity, activate protein kinase C in vitro and inhibit phorbol ester binding to the enzyme. In intact cells, the bryostatins induce some phorbol ester responses, such as neutrophil activation, but paradoxically they not only fail to induce other responses, e.g., differentiation in HL-60 promyelocytic leukemia ...