Abstract
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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Animals
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Animals, Genetically Modified
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Dishevelled Proteins
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Drosophila / embryology
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Drosophila / genetics
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Drosophila / metabolism*
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Genes, Insect
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MAP Kinase Signaling System
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Mesoderm / embryology
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Mesoderm / metabolism
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Models, Biological
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Mutation
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Receptors, Notch / genetics
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Receptors, Notch / metabolism*
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Signal Transduction
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Wnt Proteins / genetics
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Wnt Proteins / metabolism*
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Wnt1 Protein / genetics
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Wnt1 Protein / metabolism*
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ras Proteins / genetics
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ras Proteins / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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Dishevelled Proteins
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Drosophila Proteins
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N protein, Drosophila
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Phosphoproteins
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Receptors, Notch
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Wnt Proteins
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Wnt1 Protein
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cno protein, Drosophila
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dsh protein, Drosophila
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wg protein, Drosophila
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ras Proteins