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The gastrin and cholecystokinin receptors mediated signaling network: a scaffold for data analysis and new hypotheses on regulatory mechanisms

Tripathi, Sushil; Flobak, Åsmund; Chawla, Konika; Baudot, Anaïs; Bruland, Torunn; Thommesen, Liv; Kuiper, Martin Tremen R.; Lægreid, Astrid
Journal article, Peer reviewed
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URI
http://hdl.handle.net/11250/2358272
Date
2015
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  • Institutt for biologi [1657]
  • Institutt for klinisk og molekylær medisin [2016]
  • Publikasjoner fra CRIStin - NTNU [19961]
Original version
BMC Systems Biology 2015, 9(40)   10.1186/s12918-015-0181-z
Abstract
Background: The gastrointestinal peptide hormones cholecystokinin and gastrin exert their biological functions via

cholecystokinin receptors CCK1R and CCK2R respectively. Gastrin, a central regulator of gastric acid secretion, is

involved in growth and differentiation of gastric and colonic mucosa, and there is evidence that it is pro-carcinogenic.

Cholecystokinin is implicated in digestion, appetite control and body weight regulation, and may play a role in several

digestive disorders.

Results: We performed a detailed analysis of the literature reporting experimental evidence on signaling pathways

triggered by CCK1R and CCK2R, in order to create a comprehensive map of gastrin and cholecystokinin-mediated

intracellular signaling cascades. The resulting signaling map captures 413 reactions involving 530 molecular species,

and incorporates the currently available knowledge into one integrated signaling network. The decomposition of the

signaling map into sub-networks revealed 18 modules that represent higher-level structures of the signaling map.

These modules allow a more compact mapping of intracellular signaling reactions to known cell behavioral outcomes

such as proliferation, migration and apoptosis. The integration of large-scale protein-protein interaction data to this

literature-based signaling map in combination with topological analyses allowed us to identify 70 proteins able to

increase the compactness of the map. These proteins represent experimentally testable hypotheses for gaining new

knowledge on gastrin- and cholecystokinin receptor signaling. The CCKR map is freely available both in a downloadable,

machine-readable SBML-compatible format and as a web resource through PAYAO (http://sblab.celldesigner.org:18080/

Payao11/bin/).

Conclusion: We have demonstrated how a literature-based CCKR signaling map together with its protein interaction

extensions can be analyzed to generate new hypotheses on molecular mechanisms involved in gastrin- and

cholecystokinin-mediated regulation of cellular processes.
Publisher
BioMed Central
Journal
BMC Systems Biology

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