When pathways collide: collaboration and connivance among signalling proteins in development View Full Text


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Article Info

DATE

2010-05-12

AUTHORS

Helen McNeill, James R. Woodgett

ABSTRACT

Key PointsComplex organisms rely on a small number of signalling pathways to regulate all of their responses to developmental and environmental cues. These pathways achieve considerable levels of diversity and selectivity through extensive integration and crosstalk.In addition to being small in number, many components of signalling pathways are shared among multiple systems. This creates the need for mechanisms to allow the insulation of signals and discrimination of outcomes.Using the Wnt and Hippo signalling pathways as examples, there are multiple mechanisms whereby pathways influence each other yet retain their own specificity. Through feedback loops, pathway duration and intensity is often tightly controlled. Loss of such controls can lead to chronic signalling and various diseases.Species conservation of the key regulatory pathways is extensive, allowing extrapolation of overall topologies. However, rigorous genetic analysis of Drosophila melanogaster and nematodes has also revealed that interactions are often indirect and has uncovered distinct functions of many components.The fact that more than one pathway may share a common protein does not mean that these proteins are common nodes of signal transduction between the pathways. Indeed, this is typically not the case because of sequestration of molecules through scaffolds and complexes. However, the use of chemical inhibitors or RNA interference to common components breaks down these natural barriers.Building signalling systems on several common elements probably does provide a fundamental level of coordination by allowing the re-balancing of multiple pathways should one important component become limiting. More... »

PAGES

404-413

References to SciGraph publications

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  • 2005-12-11. The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis in NATURE CELL BIOLOGY
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  • 1982-04. The role of protein phosphorylation in neural and hormonal control of cellular activity in NATURE
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  • 1999-06-24. The TAK1–NLK–MAPK-related pathway antagonizes signalling between β-catenin and transcription factor TCF in NATURE
  • 2009-11-22. YAP-dependent induction of amphiregulin identifies a non-cell-autonomous component of the Hippo pathway in NATURE CELL BIOLOGY
  • 2009-06-17. Proximal events in Wnt signal transduction in NATURE REVIEWS MOLECULAR CELL BIOLOGY
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    URI

    http://scigraph.springernature.com/pub.10.1038/nrm2902

    DOI

    http://dx.doi.org/10.1038/nrm2902

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1016461925

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20461097


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