A network map of the gastrin signaling pathway

Subbannayya, Yashwanth; Anuja, Kumari; Advani, Jayshree; Ojha, Urmesh K.; Nanjappa, Vishalakshi; George, B; Sonawane, Avinash; Kumar, Rekha V.; Ramaswamy, Girija; Pandey, Akhilesh; Somani, Babu Lal; Raju, Rajesh

doi:10.1007/s12079-014-0224-z

Cited by 12 publications

(10 citation statements)

References 54 publications

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“…In the past decade, several manually constructed maps of signaling events have been published [ 16 – 25 ], each providing solid foundations for a systems understanding of the signaling mechanisms. The present work extends this approach to the domain of CCKR signaling by providing a comprehensive literature-based CCKR signaling map that comprises 530 molecular species and 431 reactions, considerably extending previously compiled knowledge on CCK2R signaling [ 10 , 26 ] including CCK1R downstream events.…”

Section: Introductionmentioning

confidence: 84%

“…However, the CCKR map constitutes a vastly more comprehensive and integrated model, providing detailed signaling reactions linking the receptors CCK1R and CCK2R all the way to regulated genes and cellular responses. For comparison, the recently published gastrin signaling map [ 26 ] comprises approximately half of the molecules and only a quarter of the reactions presented in our CCKR map. Similarly, knowledge currently in Reactome covers less than 5 % of the pathway details presented here.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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BackgroundThe 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.ResultsWe 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/).ConclusionWe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-015-0181-z) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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“…As an example, three of the top 10 genes upregulated at 4 days have gene ontology terms associated with G protein-coupled receptor (GPCR) signaling pathways: GAST, GPR84, and MC5R. While the function of these genes in controlling IVD homeostasis or pathology is largely unknown, 163 they have been investigated in tissues and disease states including stomach mucosa/gastrointestinal disorders, 164,165 leukocytes/leukemia, 166,167 and kidney cells/kidney function, 168,169 respectively. Additionally, the products of these three genes, while not binding to TEAD directly, connect through several intracellular pathways through major signaling proteins including AKT and ABL1.…”

Section: Downregulated Gene Sets Identified Through Gene Set Enrichmentioning

confidence: 99%

Verteporfin treatment controls morphology, phenotype, and global gene expression for cells of the human nucleus pulposus

et al. 2020

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Cells of the nucleus pulposus (NP) are essential contributors to extracellular matrix synthesis and function of the intervertebral disc. With age and degeneration, the NP becomes stiffer and more dehydrated, which is associated with a loss of phenotype and biosynthetic function for its resident NP cells. Also, with aging, the NP cell undergoes substantial morphological changes from a rounded shape with pronounced vacuoles in the neonate and juvenile, to one that is more flattened and spread with a loss of vacuoles. Here, we make use of the clinically relevant pharmacological treatment verteporfin (VP), previously identified as a disruptor of yes-associated protein-TEA domain family member-binding domain (TEAD) signaling, to promote morphological changes in adult human NP cells in order to study variations in gene expression related to differences in cell shape. Treatment of adult, degenerative human NP cells with VP caused a shift in morphology from a spread, fibroblastic-like shape to a rounded, clustered morphology with decreased transcriptional activity of TEAD and serum-response factor. These changes were accompanied by an increased expression of vacuoles, NP-specific gene markers, and biosynthetic activity. The contemporaneous observation of VP-induced

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“…Though the signaling pathway map of IL-18 is available in KEGG and Reactome pathway database, it currently provides only a generic view of the signaling modules regulated by IL-18. In the current study, we developed a resource of signaling events mediated by IL-18/IL-18R in similar lines to earlier reports on comprehensive signaling maps (Bhat et al 2019;Pinto et al 2018;Subbannayya et al 2014). Our resource contains the complete cascade of IL-18 signaling, including 319 molecules and 402 reactions stimulated by IL-18 through manual annotation of the data mined from the publicly available literature.…”

Section: Introductionmentioning

confidence: 90%

A comprehensive pathway map of IL-18-mediated signalling

Rex

Agarwal

Prasad

et al. 2019

J. Cell Commun. Signal.

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Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines and was initially described as an IFN-γ-inducing factor derived from anti-CD3-stimulated T-helper (Th)1 cells. IL-18 plays a significant role in the activation of hematopoietic cell types mediating both Th1 and Th2 responses and is the primary inducer of interferon-γ in these cells. The biological activity of IL-18 is mediated through its binding to the IL-18 receptor complex and activation of nuclear factor-κB (NF-κB), culminating in the production and release of several cytokines, chemokines, and cellular adhesion molecules. In certain cell types, IL-18 also activates mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase/ AKT serine/threonine kinase (PI3K/AKT) signaling modules leading to the production and release of proinflammatory cytokines. IL-18-mediated signaling acts as one of the vital components of the immunomodulatory cytokine networks involved in host defense, inflammation, and tissue regeneration. Albeit its biomedical importance, a comprehensive resource of IL-18 mediated signaling pathway is currently lacking. In this study, we report on the development of an integrated pathway map of IL-18/IL-18R signaling. The pathway map was developed through literature mining from published literature based on manual curation guidelines adapted from NetPath and includes information on 16 protein-protein interaction events, 38 enzyme-catalysis events, 12 protein translocation events, 26 activations/inhibition events, transcriptional regulators, 230 gene regulation events and 84 induced protein expression events. The IL-18 signaling pathway can be freely accessed through the WikiPathways database (https://www.wikipathways.org/index.php/Pathway:WP4754).

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A network map of the gastrin signaling pathway

Cited by 12 publications

References 54 publications

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

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

Verteporfin treatment controls morphology, phenotype, and global gene expression for cells of the human nucleus pulposus

A comprehensive pathway map of IL-18-mediated signalling

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