Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.
FEMS Yeast Res. 2010 Mar;10(2):177-87. doi: 10.1111/j.1567-1364.2009.00598.x. Epub 2010 Dec 10.
The genome of the yeast Saccharomyces cerevisiae encodes two cyclic AMP (cAMP) phosphodiesterases, a low-affinity one, Pde1, and a high-affinity one, Pde2. Pde1 has been ascribed a function for downregulating agonist-induced cAMP accumulation in a protein kinase A (PKA)-governed negative feedback loop, whereas Pde2 controls the basal cAMP level in the cell. Here we show that PKA regulates the localization and protein concentration of Pde2. Pde2 is accumulated in the nucleus in wild-type cells growing on glucose, or in strains with hyperactive PKA. In contrast, in derepressed wild-type cells or cells with attenuated PKA activity, Pde2 is distributed over the nucleus and cytoplasm. We also show evidence indicating that the Pde2 protein level is positively correlated with PKA activity. The increase in the Pde2 protein level in high-PKA strains and in cells growing on glucose was due to its increased half-life. These results suggest that, like its low-affinity counterpart, the high-affinity phosphodiesterase may also play an important role in the PKA-controlled feedback inhibition of intracellular cAMP.
酵母酿酒酵母的基因组编码两种环腺苷酸（cAMP）磷酸二酯酶，一种是低亲和力的 Pde1，另一种是高亲和力的 Pde2。Pde1 被认为在蛋白激酶 A（PKA）调控的负反馈环中下调激动剂诱导的 cAMP 积累，而 Pde2 控制细胞中的基础 cAMP 水平。在这里，我们表明 PKA 调节 Pde2 的定位和蛋白浓度。在葡萄糖上生长的野生型细胞或 PKA 超活跃的菌株中，Pde2 积累在核内。相比之下，在去阻遏的野生型细胞或 PKA 活性减弱的细胞中，Pde2 分布在核和细胞质中。我们还提供了证据表明，Pde2 蛋白水平与 PKA 活性呈正相关。高 PKA 菌株和在葡萄糖上生长的细胞中 Pde2 蛋白水平的增加是由于其半衰期延长所致。这些结果表明，与低亲和力的磷酸二酯酶一样，高亲和力磷酸二酯酶可能在 PKA 控制的细胞内 cAMP 反馈抑制中也发挥重要作用。
