Further characterization of tumor-promoter-mediated activation of protein kinase C

Couturier, Anne; S, Bazgar; Castagna, Monique

doi:10.1016/0006-291x(84)90203-1

Cited by 84 publications

(19 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thereafter, in biochemical and theoretical studies, we have shown that the hydroxyl group in the 3-position of diacylglycerol was required for activity, and we have emphasized the importance of its orientation into the lipid bilayer [8,9]. In addition, protein kinase C activation has been described as stereospecific [10,11] and therefore 1,2-sn appeared to be the active configuration of diacylglycerol.…”

Section: 2-o-didecanoyl-rac-glycerol;mentioning

confidence: 99%

“…In addition, protein kinase C activation has been described as stereospecific [10,11] and therefore 1,2-sn appeared to be the active configuration of diacylglycerol. Moreover, it has been reported that esterification with saturated short-chain fatty acid or unsaturated long-chain fatty acid led to greater efficiency of these compounds [8,12,13].…”

Section: 2-o-didecanoyl-rac-glycerol;mentioning

confidence: 99%

See 1 more Smart Citation

Alkyl analogs of diacylglycerol as activators of protein kinase C

et al. 1987

Self Cite

View full text Add to dashboard Cite

Diacylglycerols which activate protein kinase C have the 1,2‐sn configuration. Short‐chain saturated fatty acids or long‐chain unsaturated fatty acids are required for supporting the potency of these lipids. Using alkyl analogs such as 1‐O‐decyl‐2‐O‐decanoylglycerol, 1‐O‐decanoyl‐2‐O‐decylglycerol, 1,2‐O‐didecyl‐glycerol, 1‐O‐hexadecyl‐2‐O‐acetylglycerol and 1‐O‐decyl‐2‐O‐acetylglycerol, we showed that the ether bond was consistently associated with a loss of activity to varying extents. The results suggest that the ester bond in the 1‐position is a major determinant of diacylglycerol‐mediated protein kinase activation.

show abstract

Section: 2-o-didecanoyl-rac-glycerol;mentioning

confidence: 99%

Section: 2-o-didecanoyl-rac-glycerol;mentioning

confidence: 99%

Alkyl analogs of diacylglycerol as activators of protein kinase C

et al. 1987

Self Cite

View full text Add to dashboard Cite

show abstract

“…TPA as well as RPA and mezerein, all of which are protent protein kinase C activators (9)(10)(11), suppressed the first prominent peak of ODC induction caused by medium-replace ment, i.e. serum factor(s), in A431 human epidermoid carcinoma cells.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Regulation of Serum Factor(s)-Caused Ornithine Decarboxylase Induction by the Protein Kinase C System in A431 Human Epidermoid Carcinoma Cells.

et al. 1991

View full text Add to dashboard Cite

Replacement of the culture medium with fresh medium containing 10% fetal calf serum caused ornithine decarboxylase (ODC) induction in A431 human epidermoid carcinoma cells. Two peaks of ODC activity were observed at 5 and 14 hr after the medium replacement. The peak activity observed at 5 hr was more promi nent than that at 14 hr. The first peak of ODC induction was suppressed by a potent protein kinase C activator, 12-O-tetradecanoylphorbol-13-acetate (TPA), in a concentration-dependent manner. The second peak, however, was not suppressed by TPA. Other potent protein kinase C activators, such as mezerein and 12-0 retinoylphorbol-13-acetate, also suppressed the first peak of ODC induction. Synthetic diacylglycerols, 1,2-dioctanoyl-sn-glycerol and 1-oleoyl-2-acetylglycerol, did not inhibit the serum factor(s)-caused ODC induction. Phorbol-13-acetate, an inactive phorbol ester, also failed to inhibit the ODC induction. The growth of A431 cells was slightly suppressed by TPA. In protein kinase C down-regulated cells, TPA failed to inhibit the serum factor(s)-caused ODC induction. These results suggest that the serum factor(s)-caused ODC induction in A431 cells is negatively regulated by the protein kinase C system, which may not be activated by exogenous diacylglycerols.

show abstract

“…However, the role of calcium has been reconsidered since the demonstration that phorbol ester (TPA) can substitute for diacylglycerol and activate the enzyme directly [20]. While, in the initial studies, it was found that calcium increased the affinity for phospholipids as in the case of the activation by diacylglycerol [20], later work suggested that PKc can be activated by TPA in the presence of only tracer amounts of Ca2+ [21,25,26] or that Ca2+ is not needed [22,28]. In addition, in several cellular systems some of the TPA effects were obtained in the absence of Ca2 + mobilization, leading to the conclusion that only tracer amounts of Ca2+, if any, are sufficient for PKc activation by TPA [23,24,291.…”

Section: Discussionmentioning

confidence: 99%

“…On the basis of these results it appears that calcium could play a role not only in the activation of the PKc as was proposed earlier, but also in the selection of substrates that are phosphorylated by the PKc. Calcium could act by changing the conformation of the enzyme or its complex with phospholipids [21] allowing the access of the specific substrate. Another possibility is that calcium also acts on the substrates either through a binding mechanism or through a conformational change of proteins which renders them ready for phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

Characteristics of thyroid protein kinase C

Omri

Pavlović-Hournac

1987

European Journal of Biochemistry

View full text Add to dashboard Cite

Thyroid protein kinase C (PKc) from cytosols of porcine and rat thyroid glands has been characterized using histone H1 or endogenous proteins as substrates. As in many other tissues histone HI is by far the preferred exogenous substrate of thyroid PKc. Kinetic studies with H1 showed that, compared to rat thyroids, porcine glands are particularly rich in PKc, the predominant kinase activity in this tissue. The CAMP-dependent protein kinase (PKa) level, on the contrary, is very similar in both rat and porcine thyroids. Consequently, for the same type of tissue, there may be great species differences in the PKc level and the ratios between PKc and PKa kinase activities.Chromatographic properties of thyroid PKc are similar to those described in other tissues (one major peak followed by a small shoulder) except that elution of the main peak can vary depending on the nature of the salt gradient ( M 55 mM for NaCl and 15 mM for sodium phosphate). In the first case PKc is completely separated from the PKa activity, in the second it is coeluted with the peak of PKa type I.The one-dimensional PAGE pattern of proteins phosphorylated by porcine PKc is very similar to the pattern obtained by rat enzyme. Protein bands of 18 kDa, 22-25 kDa and 32-36 kDa are specific substrates of the thyroid PKc, after in vitro phosphorylation of cytosol proteins.A great difference in Ca2+ requirement for PKc activation was noted, depending whether histone HI or endogenous proteins were substrates. As in other tissues, calcium was absolutely necessary for phosphorylation of histone H1 by PKc. The addition of calcium was not absolutely necessary when endogenous proteins were the substrates, either for the activation of the enzyme or for phosphorylation of the PKc-specific substrates. Almost the same rate of phosphorylation was obtained with or without calcium in the incubation medium. However the one-dimensional PAGE pattern of phosphorylated proteins was different in the presence or absence of calcium. While addition of calcium was not absolutely necessary for the phosphorylation of a great number of proteins by the PKc, its presence was indispensable for the phosphorylation of certain endogenous substrates. However, calcium alone, in the absence of phospholipids had no effect on the phosphorylation of these proteins.Endogenous proteins, phosphorylated by the PKc only when calcium was present, were resolved by the twodimensional PAGE into several distinct spots with molecular masses of 32 -35 kDa and PI range of 5 -7.5.Our results suggest that only very low concentrations of Ca2+, if any, are sufficient for the phosphorylation of many endogenous substrates. Higher Ca2 + concentrations are necessary for the phosphorylation of specific proteins. It could be that modulation of Ca2+ concentration plays a role in the selection of protein substrates phosphorylated by PKc.

show abstract

Further characterization of tumor-promoter-mediated activation of protein kinase C

Cited by 84 publications

References 9 publications

Alkyl analogs of diacylglycerol as activators of protein kinase C

Alkyl analogs of diacylglycerol as activators of protein kinase C

Inhibitory Regulation of Serum Factor(s)-Caused Ornithine Decarboxylase Induction by the Protein Kinase C System in A431 Human Epidermoid Carcinoma Cells.

Characteristics of thyroid protein kinase C

Contact Info

Product

Resources

About