1. In the pleural mechanoafferent sensory neurons of Aplysia, serotonin (5-HT)-induced spike broadening consists of at least two components: a cAMP and protein kinase A (PKA)-dependent, rapidly developing component and a protein kinase C (PKC)-dependent, slowly developing component. Voltage-clamp experiments were conducted to identify currents that are modulated by PKC and thus may contribute t...

The unesterified, water-soluble compound phorbol, which does not act as a promoting agent for skin carcinogenesis when applied topically (although phorbol esters extracted from croton seed oil display pronounced activity), was tested in female SWR mice for promoting action by the systemic route, in the hope of overcoming a suspected solubility barrier in the skin. The results were negative. A h...

Treatment of U-937 GTB cells with tumor-promoting phorbol esters induced adherence of the cells to plastic, with a t1/2 of 20 min. The ED50 was determined to 3.3 nM for phorbol-12,13-dibutyrate and 0.3 nM for 12-O-tetradecanoyl-4 beta-phorbol-13-acetate, whereas the non-tumor-promoting analogue 12-O-tetradecanoyl-4 alpha-phorbol-13-acetate was ineffective at concentrations up to 100 nM. The adh...

Phorbol esters increase glucose (Glc) uptake and utilization in a variety of cell types, and, in some cells, these changes have been attributed to increased Glc phosphorylation and better functional coupling of hexokinases (HKs) to facilitative Glc transporters. Phorbol esters are potent mesangial cell mitogens, but their effects on HK-catalyzed Glc phosphorylation and metabolism are unknown. W...

Alterations in patterns of protein phosphorylation after exposure to phorbol esters were compared in chicken embryo fibroblasts and KD cells (a human fibroblast line) by two-dimensional gel electrophoresis. A substantial increase in phosphorylation was observed of a major, markedly acidic protein of pI = 4.5 in two-dimensional gels of each cell type. However, the apparent molecular weights of t...

1. The electrophysiological properties of the sensory neurons that mediate withdrawal reflexes in Aplysia are modulated by a number of second messengers. For example, the second messengers adenosine 3',5'-cyclic monophosphate (cAMP) and arachidonic acid modulate the S-K+ current (IK,S) and the calcium-activated K+ current (IK,Ca). Recent evidence suggests that protein kinase C (PKC) may also be...

Protein kinase D (PKD) is a serine/threonine kinase that binds phorbol esters in a phospholipid-dependent manner via a tandemly repeated cysteine-rich, zinc finger-like motif (the cysteine-rich domain, CRD). Here, we examined whether the individual cysteine-rich motifs of the CRD of PKD (referred to as cysl and cys2) are functionally equivalent in mediating phorbol ester binding both in vivo an...

The ability of phorbol derivatives to function as stimulating agents for superoxide (O2-) release by guinea pig neutrophils has been evaluated and compared to the known ability of each compound to activate protein kinase C. Those that activate the kinase also stimulate O2- release, while those that are inactive with respect to the kinase have no effect on O2- release. The same correlation was o...

Phorbol esters stimulate differentiation of certain human leukemic cell lines. Although activation of protein kinase C may mediate certain effects of phorbol esters, controversy exists as to the role of protein kinase C activation in phorbol ester-induced differentiation. Retinole acid modu lates responses to phorbol esters in several cell types. Retinoic acid has also been found to alter prote...