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

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dc.contributor.author Tripathi, Sushil
dc.contributor.author Flobak, Åsmund
dc.contributor.author Chawla, Konika
dc.contributor.author Baudot, Anaïs
dc.contributor.author Bruland, Torunn
dc.contributor.author Thommesen, Liv
dc.contributor.author Kuiper, Martin
dc.contributor.author Lægreid, Astrid
dc.date.accessioned 2015-07-24T03:55:03Z
dc.date.available 2015-07-24T03:55:03Z
dc.date.issued 2015-07-24
dc.identifier.citation BMC Systems Biology. 2015 Jul 24;9(1):40
dc.identifier.uri http://hdl.handle.net/10138/155699
dc.description.abstract 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.
dc.publisher BioMed Central
dc.title The gastrin and cholecystokinin receptors mediated signaling network: a scaffold for data analysis and new hypotheses on regulatory mechanisms
dc.date.updated 2015-07-24T03:55:03Z
dc.language.rfc3066 en
dc.rights.holder Tripathi et al.
dc.type.uri http://purl.org/eprint/entityType/ScholarlyWork
dc.type.uri http://purl.org/eprint/entityType/Expression
dc.type.uri http://purl.org/eprint/type/JournalArticle

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