title: The gastrin and cholecystokinin receptors mediated signaling network: a scaffold for data analysis and new hypotheses on regulatory mechanisms.
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/).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), N-7489, Trondheim, Norway. sushil.tripathi@helsinki.fi.
authors.forename: Sushil
authors.initials: S
authors.lastname: Tripathi
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), N-7489, Trondheim, Norway. asmund.flobak@ntnu.no.
authors.forename: Åsmund
authors.initials: Å
authors.lastname: Flobak
authors.affiliation: Department of Biology, Norwegian University of Science and Technology (NTNU), N-7491, Trondheim, Norway. konika.chawla@ntnu.no.
authors.forename: Konika
authors.initials: K
authors.lastname: Chawla
authors.affiliation: I2M, Marseilles Institute of Mathematics CNRS - AMU, Case 907, 13288, Marseille, Cedex 9, France. anais.baudot@univ-amu.fr.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Baudot
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), N-7489, Trondheim, Norway. torunn.bruland@ntnu.no.
authors.forename: Torunn
authors.initials: T
authors.lastname: Bruland
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), N-7489, Trondheim, Norway. liv.thommesen@ntnu.no.|Department of Technology, Sør-Trøndelag University College, N-7004, Trondheim, Norway. liv.thommesen@ntnu.no.
authors.forename: Liv
authors.initials: L
authors.lastname: Thommesen
authors.affiliation: Department of Biology, Norwegian University of Science and Technology (NTNU), N-7491, Trondheim, Norway. martin.kuiper@ntnu.no.
authors.forename: Martin
authors.initials: M
authors.lastname: Kuiper
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), N-7489, Trondheim, Norway. astrid.lagreid@ntnu.no.|Institute of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), N-7489, Trondheim, Norway. astrid.lagreid@ntnu.no.
authors.forename: Astrid
authors.initials: A
authors.lastname: Lægreid
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D019295:Computational Biology; D005755:Gastrins / Q000378:metabolism*; D042541:Intracellular Space / Q000378:metabolism; D025941:Protein Interaction Mapping; D051381:Rats; D043887:Receptor, Cholecystokinin B / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D005755:Gastrins; D043887:Receptor, Cholecystokinin B