The chemokine receptors CCR5 and CXCR4 are major co-receptors/receptors for the CD4-dependent and CD4-independent entry of human and simian immunodeficiency viruses. The chemokines that bind and activate these receptors can inhibit the entry of viruses that use the respective co-receptor molecules. Chemokine-induced co-receptor internalisation is a significant component of the mechanism through...

Recent work from our laboratory has demonstrated that phorbol esters known to stimulate protein kinase C (PKC) also stimulate acetylcholine (ACh) secretion by an action at a strategic component of the secretory apparatus [ J Physiol (Lond) 501:41-48]. In an attempt to determine whether the stimulatory effects of phorbols are mediated by PKC, we examined the effects of several PKC antagonists on...

Ca2+-dependent and phospholipid-dependent protein kinase (PKC) is a receptor for and is activated by phorbol esters. This enzyme is reportedly involved in the mechanism of superoxide anion (O2-) production and the release of intracellular granule contents from human neutrophils. As previously reported by others, we found that greater than 75% of the total cellular PKC activity existed in a solu...

Tumor-promoting phorbol esters such as 1 2-0-tetradecanoyl-phorbol-1 3-acetate (TPA) or phorbol-12.1 3-didecanoate (PDD) stimulate freshly isolated murine bone marrow cells in vitro to form colonies of myeloid cells in semisolid medium without added colony-stimulating factors (CSF). while phorbol and its nonpromoting derivatives do not induce marrow colony formation. TPA-stimulated colonies are...

The phorbol ester analog, mezerein, is a weak complete and Stage 1 tumor promoter; however, it is as potent as the most active phorbol esters as a second stage promoter and inflammatory agent. Therefore, mezerein is a useful compound for studying responses associated with Stage 1 or Stage 2 promotion. In this paper, we show that in G-292 osteosarcoma cells in culture, mezerein is 25-fold more p...

We have compared the activities of aplysiatoxin and debromoaplysiatoxin, two polyacetate marine algae toxins, with teleocidin, a tumor-promoting indole alkaloid from Streptomyces, with respect to inhibition of specific binding of epidermal growth factor, and phorbol-12,13-dibutyrate to their respective receptors and ability to stimulate the release of radioactivity from cells prelabeled with ch...

We have studied the expression of mRNA encoding adenosine deaminase (ADA; EC 3.5.4.4), purine nucleoside phosphorylase (PNP; EC 2.4.2.1), and terminal deoxynucleotidyltransferase (TdT; EC 2.7.7.31) in different leukemic cell lines of B- and T-cell lineage. Incubation of leukemic cells in the presence of the phorbol esters, 12-O-tetradecanoyl-phorbol-13-acetate or phorbol 12,13-dibutyrate, resul...

We have compared the activities of aplysiatoxin and debromoaplysiatoxin, two polyacetate marine algae toxins, with teleocidin, a tumor-promoting indole alkaloid from Streptomyces, with respect to inhibition of specific binding of epidermal growth factor, and phorbol-12,13-dibutyrate to their respective receptors and ability to stimulate the release of radioactivity from cells prelabeled with ch...

Glucose and other secretagogues are thought to activate a variety of protein kinases. This study was designed to unravel the sites of action of protein kinase A (PKA) and protein kinase C (PKC) in modulating insulin secretion. By using high time resolution measurements of membrane capacitance and flash photolysis of caged Ca(2+), we characterize three kinetically different pools of vesicles in ...

Integrins are transmembrane proteins involved in cell-cell and cell-extracellular-matrix interactions. The affinity and avidity of integrins for their ligands change in response to cytoplasmic signals. This 'inside-out' activation has been reported to occur also with beta2 integrins (CD18). The beta2 integrin subunit has previously been shown to become phosphorylated in T lymphocytes on cytopla...