Bouzinba-Segard H, Fan X T, Perderiset M, Castagna M
INSERM U-268, Hôpital Paul-Brousse, Villejuif, France.
Biochem Biophys Res Commun. 1994 Oct 14;204(1):112-9. doi: 10.1006/bbrc.1994.2433.
All-trans retinoic acid (RA) activates brain protein kinase C (PKC) in a unique fashion. Co-factors such as Ca2+ or PtdSer are not required for histone phosphorylation. Binding experiments have provided evidence that RA does not act as a phorbol-ester-like activator. However, phorbol esters synergistically enhance this activation in a dose-dependent manner and increase the reaction rate up to five-fold when combined with 10 microM RA. Phospholipid-interacting drugs such as phenothiazines and 1-N-(6 aminohexyl) 5-chloro-1-naphthalene-sulfonamide (W7), which compete with PtdSer and inhibit phorbol ester/PtdSer-mediated activation, have potentiating effects on the RA-mediated reaction. RA elicits Ca(2+)-dependent PKC autophosphorylation. The activation resulting from the combined treatment with PtdSer and RA is more than additive in the presence of Ca2+, indicating that PtdSer- and RA-binding sites are distinct. RA shares several characteristics of activation with sodium deoxycholate and arachidonic acid. These present results suggest that the direct activation of PKC may have physiological and/or pharmacological relevance in the signaling triggered by retinoids.
全反式维甲酸（RA）以独特方式激活脑蛋白激酶C（PKC）。组蛋白磷酸化不需要Ca2+或磷脂酰丝氨酸（PtdSer）等辅助因子。结合实验已提供证据表明RA并非作为佛波酯样激活剂起作用。然而，佛波酯以剂量依赖性方式协同增强这种激活作用，并且当与10微摩尔RA联合使用时，可将反应速率提高至五倍。与PtdSer竞争并抑制佛波酯/PtdSer介导激活的磷脂相互作用药物，如吩噻嗪和1-N-（6-氨基己基）5-氯-1-萘磺酰胺（W7），对RA介导的反应具有增强作用。RA引发Ca(2+)依赖性PKC自身磷酸化。在存在Ca2+的情况下，PtdSer与RA联合处理所产生的激活作用大于两者单独作用之和，表明PtdSer结合位点与RA结合位点不同。RA与脱氧胆酸钠和花生四烯酸具有一些激活特性。这些目前的结果表明，PKC的直接激活可能在类视黄醇触发的信号传导中具有生理和/或药理学相关性。
