Acs P, Szallasi Z, Kazanietz M G, Blumberg P M
Molecular Mechanisms of Tumor Promotion Section, National Cancer Institute, Bethesda, MD 20892, USA.
Biochem Biophys Res Commun. 1995 Nov 2;216(1):103-9. doi: 10.1006/bbrc.1995.2597.
14-3-3 proteins are ubiquitous in eukaryotes associated with many fundamental functions in signal transduction pathways and cell cycle regulation. Protein kinase C comprises a large family of serine/threonine protein kinases that are involved in cell growth and differentiation. Different protein kinase C isozymes have distinct roles in signal transduction pathways; protein kinase C epsilon is of particular interest because its overexpression leads to oncogenic transformation. The 14-3-3 protein has been reported to regulate the activity of protein kinase C, although the nature of its effect is equivocal. In this study we report the differential activation of various protein kinase C isoforms by 14-3-3 zeta protein. The classical isozymes show approximately a twofold activation, protein kinase C delta shows no significant increase in activity, whereas protein kinase C epsilon, another novel isozyme, is highly activated. This activation shows strong positive cooperativity with a Hill coefficient of 6.1 +/- 0.2.
14-3-3蛋白在真核生物中广泛存在，与信号转导通路和细胞周期调控中的许多基本功能相关。蛋白激酶C由一大类丝氨酸/苏氨酸蛋白激酶组成，参与细胞生长和分化。不同的蛋白激酶C同工酶在信号转导通路中具有不同的作用；蛋白激酶Cε特别受关注，因为其过表达会导致致癌转化。据报道，14-3-3蛋白可调节蛋白激酶C的活性，但其作用性质尚不明确。在本研究中，我们报道了14-3-3ζ蛋白对各种蛋白激酶C同工型的差异激活作用。经典同工型显示出约两倍的激活，蛋白激酶Cδ的活性没有显著增加，而另一种新型同工型蛋白激酶Cε则被高度激活。这种激活表现出强烈的正协同性，希尔系数为6.1±0.2。
