PDE4D phosphorylation: A coincidence detector integrating multiple signaling pathways

Cell Signal. 2016 Jul;28(7):719-24. doi: 10.1016/j.cellsig.2015.11.001. Epub 2015 Nov 10.


In Eukaryotes, more than 100 different phosphodiesterase (PDE) proteins serve to fine-tune cyclic nucleotide (cAMP and cGMP) signals and contribute to specificity of signaling. In mammals, PDEs are divided into 11 families, of which PDE4 represents the largest family. Four genes (pde4a, pde4b, pde4c and pde4d) encode for this class of enzymes in mammals and give rise to more than 20 variants. Within this family of genes, PDE4D was discovered on the basis of its regulatory properties and its induction by hormones and cAMP. PDE4D has often been used as the prototype PDE4 and large body of work has been generated on the biochemical, pharmacological, and physiological properties of this enzyme. This review covers the regulation of PDE4D by phosphorylation, the impact of this regulation in the context of the structure of this protein, and the functional consequences of this complex pattern of posttranslational modifications.

Keywords: PDE4D; Phosphodiesterase; Phosphorylation; Posttranslational modification.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cyclic AMP / metabolism
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / chemistry
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism*
  • Feedback, Physiological
  • Humans
  • Phosphorylation
  • Protein Domains
  • Signal Transduction*


  • Cyclic AMP
  • Cyclic Nucleotide Phosphodiesterases, Type 4