Several novel phorbol esters were prepared with polar functional groups terminating their C12 and/or C13 acyl chains. Designed to be inhibitory protein kinase C (PKC) ligands, these phorbol analogues contain various polar functional groups (amide, ester, carboxylic acid, or quaternary ammonium salt) to prevent membrane insertion of the PKC-phorbol ester complex. All phorbol derivatives were syn...

An enzyme which catalyzes the following esterase reaction was isolated from mouse serum: 12-0-tetradecanoyl phorbol 13-acetate (TPA) + Ha0 + phorbol 13-acetate + tetradecanoic acid. The recovery was 0.18% of total serum protein and 820-fold purification was achieved. The enzyme is composed of a single polypeptide chain with sugar moiety; its molecular weight was estimated to be 77,000. Its suga...

Tumor-promoting phorbol esters reversibly inhibit intercellular communication between BALB/c 3T3 cells. In order to study the possible role of blocked intercellular communication in the promotion step in cell transformation, we investigated the effect of phorbol ester tumor promoters on cell transformation and intercellular communication in BALB/c 3T3 A31-1-1 cells by a dye-transfer method. Whe...

Topical application of 17 nmoles of the potent tumor promoter, 12-O-tetradecanoylphorbol-13-acetate, resulted in a stimulation of the incorporation of [(3)H]lysine into epidermal histones. Maximum incorporation occurred 24 hr after treatment, concurrent with maximum DNA synthesis. The effects of phorbol and two phorbol esters on histone synthesis were related to their tumor-promoting activities...

The possible involvement of protein kinase C and Ca2+ metabolism in the proteolytic enzyme release from schistosome cercariae was studied. Cercariae were placed in dechlorinated tap water containing 0.37 mM calcium in the small glass petri dish and exposed to the stimuli (linoleic acid, phorbol esters, and Ca2+ ionophore) with or without inhibitors of protein kinase C or Ca2+ metabolism. The pr...

Phorbol, the terpene alcohol found in the skin tumor-promoting components of croton oil, was isolated, and four diesters were synthesized from it. The tumor-promoting potencies of these compounds were tested in Charles River GDI mice and skin tumor-susceptible mice. The esters of high tumor-promoting ability (12-O-tetradecanoyl-phorbol-13acetate and phorbol-12,13-didecanoate) were effective in ...

Beta2-chimaerin, a member of the GTPase-activating proteins for the small GTP-binding protein p21Rac, possesses a single cysteine-rich domain with high homology to those implicated in phorbol ester and diacylglycerol binding in protein kinase C (PKC) isozymes. We have expressed beta2-chimaerin in Sf9 insect cells using the baculovirus expression system and determined that, like PKCs, beta2-chim...