PDE6 is an effector for the Wnt/Ca2+/cGMP-signalling pathway in development

Biochem Soc Trans. 2004 Nov;32(Pt 5):792-6. doi: 10.1042/BST0320792.


Wnt signalling in development operates via members of the Frizzleds, G-protein-coupled receptors that bind specific Wnt ligands and mediate signalling via distinct pathways. The Wnt/Ca(2+)/cGMP pathway mediated by Frizzled-2 was discovered recently. Activation of this pathway leads to increased intracellular concentrations of Ca(2+) and decreased intracellular concentrations of cGMP. The nature of the phosphodiesterase responsible for this Frizzled-2-mediated effect on cGMP levels was identified based on three separate criteria: (i) sensitivity to selective enzyme inhibitors, (ii) behaviour on chromatographic separation, and (ii) isolation by two-dimensional gels in tandem with direct mapping by MS of tryptic digests of the activity. On the basis of results from these three analyses, the cGMP-specific phosphodiesterase, PDE6, is demonstrated to be an effector for the Wnt/Ca(2+)/cGMP signalling pathway of development, which is mediated by Frizzled-2.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Cyclic GMP / metabolism*
  • Cyclic Nucleotide Phosphodiesterases, Type 6
  • Electrophoresis, Gel, Two-Dimensional
  • Frizzled Receptors
  • Gene Expression Regulation, Developmental*
  • Immunoblotting
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Peptide Mapping
  • Phosphoric Diester Hydrolases / metabolism
  • Phosphoric Diester Hydrolases / physiology*
  • Rats
  • Receptors, G-Protein-Coupled
  • Receptors, Neurotransmitter / metabolism
  • Receptors, Neurotransmitter / physiology*
  • Signal Transduction
  • Trypsin / pharmacology
  • Vision, Ocular
  • Wnt Proteins


  • Frizzled Receptors
  • Intercellular Signaling Peptides and Proteins
  • Receptors, G-Protein-Coupled
  • Receptors, Neurotransmitter
  • Wnt Proteins
  • Fzd2 protein, rat
  • Phosphoric Diester Hydrolases
  • Cyclic Nucleotide Phosphodiesterases, Type 6
  • Trypsin
  • Cyclic GMP
  • Calcium