The PDZ protein Canoe/AF-6 links Ras-MAPK, Notch and Wingless/Wnt signaling pathways by directly interacting with Ras, Notch and Dishevelled

PLoS One. 2006 Dec 20;1(1):e66. doi: 10.1371/journal.pone.0000066.


Over the past few years, it has become increasingly apparent that signal transduction pathways are not merely linear cascades; they are organized into complex signaling networks that require high levels of regulation to generate precise and unique cell responses. However, the underlying regulatory mechanisms by which signaling pathways cross-communicate remain poorly understood. Here we show that the Ras-binding protein Canoe (Cno)/AF-6, a PDZ protein normally associated with cellular junctions, is a key modulator of Wingless (Wg)/Wnt, Ras-Mitogen Activated Protein Kinase (MAPK) and Notch (N) signaling pathways cross-communication. Our data show a repressive effect of Cno/AF-6 on these three signaling pathways through physical interactions with Ras, N and the cytoplasmic protein Dishevelled (Dsh), a key Wg effector. We propose a model in which Cno, through those interactions, actively coordinates, at the membrane level, Ras-MAPK, N and Wg signaling pathways during progenitor specification.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Animals, Genetically Modified
  • Dishevelled Proteins
  • Drosophila / embryology
  • Drosophila / genetics
  • Drosophila / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Genes, Insect
  • MAP Kinase Signaling System
  • Mesoderm / embryology
  • Mesoderm / metabolism
  • Models, Biological
  • Mutation
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Signal Transduction
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • Wnt1 Protein / genetics
  • Wnt1 Protein / metabolism*
  • ras Proteins / genetics
  • ras Proteins / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Dishevelled Proteins
  • Drosophila Proteins
  • N protein, Drosophila
  • Phosphoproteins
  • Receptors, Notch
  • Wnt Proteins
  • Wnt1 Protein
  • cno protein, Drosophila
  • dsh protein, Drosophila
  • wg protein, Drosophila
  • ras Proteins