PDE6 is an effector for the Wnt/Ca2+/cGMP-signalling pathway in development.
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.
Wang
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Department of Physiology and Biophysics, Health Sciences Center, State University of New York at Stony Brook, Stony Brook, NY 11794-8661, USA. wangh@pharm.sunysb.edu
Lee
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Malbon
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; D015180:Electrophoresis, Gel, Two-Dimensional; D051157:Frizzled Receptors; D018507:Gene Expression Regulation, Developmental; D015151:Immunoblotting; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D010449:Peptide Mapping; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D014357:Trypsin / Q000494:pharmacology; D014785:Vision, Ocular; D051153:Wnt Proteins
D051157:Frizzled Receptors; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter; D051153:Wnt Proteins; C078604:Fzd2 protein, rat; D010727:Phosphoric Diester Hydrolases; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; D014357:Trypsin; D006152:Cyclic GMP; D002118:Calcium