Identification of receptors for phorbol ester tumor promoters in intact mammalian cells and of an inhibitor of receptor binding in biologic fluids.

Horowitz, Ann D.; Greenebaum, Ellen; Weinstein, I B

doi:10.1073/pnas.78.4.2315

Cited by 87 publications

(32 citation statements)

References 15 publications

(8 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ED50 for VOL. 2,1982 on May 10, 2018 by guest http://mcb.asm.org/ Downloaded from down regulation was 8 nM PDBu, which is the same as the Kd for the high-affinity PDBu binding sites in these cells (8). At PDBu concentrations above that at which the high-affinity sites should have been saturated with PDBu, no further down regulation was seen.…”

Section: When [125i]egf Binding Was Titrated Withmentioning

confidence: 86%

“…[3H]phorbol-12,13-dibutyrate (PDBu) to these "phorboid receptors" is saturable and specific, occurs in the range of physiological activity of PDBu, and is inhibited by other phorbol esters (4,8,20) and by the related compound teleocidin (24) with potencies that correlate with biological activity. In most of these studies, [3H]PDBu rather than the stronger tumor promoter 12-0-tetradecanoylphorbol-…”

mentioning

confidence: 99%

“…The phorbol esters are derived from a plant species, the Euphorbiaceae. We have previously suggested that there may be ligands normally produced by mammalian systems that bind to the phorboid receptors (8,12,25). We recently described the partial purification of a factor from human serum which inhibits the binding of [3H]PDBu to intact monolayer cultures of the rat embryo cell line CREF N (8).…”

mentioning

confidence: 99%

“…In most of these studies, [3H]PDBu rather than the stronger tumor promoter 12-0-tetradecanoylphorbol-13-acetate was used to assess specific binding, because PDBu is much less hydrophobic and therefore gives much lower nonspecific binding (4,8,20). PDBu is approximately 2-to 10-fold less potent than 12-0-tetradecanoylphorbol-1 3-acetate in in vitro assays for various biological effects (4,8,20). All of these studies suggest that binding of the phorbol esters to the phorboid receptor is the initial step in the production of the diverse physiological effects of these compounds.…”

mentioning

confidence: 99%

“…Human serum was fractionated as previously described (8). Ten milliliters of serum was applied to a 100-ml column of Blue Sepharose CL-6B (Sigma) equilibrated with PBS at 4°C.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Inhibition of phorbol ester-receptor binding by a factor from human serum.

Horowitz¹,

Greenebaum²,

Nicolaides³

et al. 1982

Mol. Cell. Biol.

Self Cite

View full text Add to dashboard Cite

It has recently been found that mammalian cells of diverse types contain high-affinity receptors for the tumor-promoting phorbol esters (3-5, 8, 10, 20-22). Binding of the tumor promoter[3H]phorbol-12,13-dibutyrate (PDBu) to these "phorboid receptors" is saturable and specific, occurs in the range of physiological activity of PDBu, and is inhibited by other phorbol esters (4,8,20) and by the related compound teleocidin (24) with potencies that correlate with biological activity. In most of these studies, [3H]PDBu rather than the stronger tumor promoter 12-0-tetradecanoylphorbol-

show abstract

Section: When [125i]egf Binding Was Titrated Withmentioning

confidence: 86%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

“…Human serum was fractionated as previously described (8). Ten milliliters of serum was applied to a 100-ml column of Blue Sepharose CL-6B (Sigma) equilibrated with PBS at 4°C.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Inhibition of phorbol ester-receptor binding by a factor from human serum.

Horowitz¹,

Greenebaum²,

Nicolaides³

et al. 1982

Mol. Cell. Biol.

Self Cite

View full text Add to dashboard Cite

show abstract

Desensitization of macrophages to stimuli which induce secretion of superoxide anion. Down‐regulation of receptors for phorbol myristate acetate

Berton

Gordon

1983

Eur J Immunol

View full text Add to dashboard Cite

The ability of cultivated mouse peritoneal macrophages (M phi) to release superoxide anion (O-2) after repeated stimulation by phorbol myristate acetate (PMA) or serum-treated zymosan (STZ) has been studied. After a maximal first stimulus bacillus Calmette-Guérin (BCG)-activated M phi released high levels of O-2, 2-fold more than thioglycollate-elicited M phi and the response ceased within 4 h. Both populations either responded again to a second challenge or displayed a refractory state which varied in duration and selectivity. Desensitization by STZ pretreatment was transient and selective whereas PMA could render M phi refractory for 3 days to PMA alone or to both agents, depending on the amount of PMA used and the conditions of stimulation. PMA induced a selective loss of specific saturable receptors for [3H]phorbol dibutyrate, a closely related agent, and receptor activity recovered with the ability to release O-2. Loss of receptors did not account for concomitant loss of the response to STZ after nonselective deactivation. Such M phi were fully viable and able to endocytose various soluble and particulate ligands vigorously, but without stimulation of the hexose monophosphate shunt or release of O-2. Our studies indicate that M phi activities can be profoundly altered by prior stimulation, that specific receptors play a role in ligand-induced desensitization and that agents such as PMA can selectively eliminate the cells' ability to generate a second respiratory burst.

show abstract

Modulation of T leukaemic cell phenotype with phorbol ester

Delia

Greaves

Newman

et al. 1982

Intl Journal of Cancer

View full text Add to dashboard Cite

A panel of monoclonal antibodies and other markers (e.g., terminal deoxynucleotidyl transferase, sheep erythrocyte rosettes, peanut agglutinin) have been used in conjunction with flow cytometry and biochemical analysis to monitor the induction of maturation in human thymic (T) leukaemic cell lines by phorbol ester (TPA). Seven cell lines underwent multiple phenotypic alterations in response to TPA but were unresponsive to synthetic thymic hormones (TP5, FTS) or to other compounds (e.g. DMSO, retinoic acid) which induce maturation in other types of leukaemia. The changes parallel those observed in normal T-cell differentiation and partly reflect alterations in glycosyl transferase activity, altered synthesis of proteins and regulation of cell surface receptors (for transferrin) associated with rapid growth and metabolism. These studies further illustrate the reversibility of maturation arrest in human leukaemia and provide support for the view that leukaemia may involve regulatory defects in the coupling of proliferation and maturation. Induction of promotion of terminal differentiation in leukaemic equivalents of T-cell precursors may provide a convenient system for the study of biochemical and molecular events involved in T-cell development and diversification.

show abstract

Identification of receptors for phorbol ester tumor promoters in intact mammalian cells and of an inhibitor of receptor binding in biologic fluids.

Cited by 87 publications

References 15 publications

Inhibition of phorbol ester-receptor binding by a factor from human serum.

Inhibition of phorbol ester-receptor binding by a factor from human serum.

Desensitization of macrophages to stimuli which induce secretion of superoxide anion. Down‐regulation of receptors for phorbol myristate acetate

Modulation of T leukaemic cell phenotype with phorbol ester

Contact Info

Product

Resources

About