The localization and concentration of the PDE2-encoded high-affinity cAMP phosphodiesterase is regulated by cAMP-dependent protein kinase A in the yeast Saccharomyces cerevisiae.
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.
Hu
Yun
Y
Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China. hu_yun@tju.edu.cn
Liu
Enkai
E
Bai
Xiaojia
X
Zhang
Aili
A
D002467:Cell Nucleus / Q000378:metabolism; D003470:Culture Media; D000242:Cyclic AMP / Q000235:genetics / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2 / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D008856:Microscopy, Fluorescence; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins
D003470:Culture Media; D029701:Saccharomyces cerevisiae Proteins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2