| 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. © 2006 Carmena et al. |
| Keywords: |
signal transduction; mitogen activated protein kinase; controlled study; unclassified drug; genetics; mutation; nonhuman; animal; metabolism; animals; animal tissue; gene; biological model; models, biological; map kinase signaling system; embryo; protein protein interaction; notch receptor; drosophila; embryo development; cell differentiation; transgenic animal; stem cell; prenatal development; receptors, notch; cell membrane; adaptor proteins, signal transducing; phosphoproteins; binding protein; ras protein; ras proteins; cell junction; wnt proteins; wnt protein; mesoderm; drosophila proteins; signal transducing adaptor protein; phosphoprotein; wnt1 protein; drosophila protein; wg protein, drosophila; genes, insect; dishevelled protein; animals, genetically modified; binding kinetics; canoe protein; canoe protein, drosophila; dishevelled proteins; notch protein, drosophila
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