A modular map of Bradykinin-mediated inflammatory signaling network

• Published in: Journal of cell communication and signaling Vol. 16; no. 2; pp. 301 - 310
• Main Authors: Rex, D. A. B., Deepak, K., Vaid, Neelanchal, Dagamajalu, Shobha, Kandasamy, Richard Kumaran, Flo, Trude Helen, Keshava Prasad, T. S.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-06-2022; John Wiley & Sons, Inc
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Biomedical and Life Sciences; Biomedicine; Blood coagulation; Bradykinin; Bradykinin storm; Catalysis; Cell Biology; Chronic pain; Diabetes mellitus; Diabetic neuropathy; Diglycerides; G protein-coupled receptors; Gene regulation; Inflammation; Inositol 1,4,5-trisphosphate receptors; Kallikrein; Kinases; Life Sciences; MAP kinase; Nitric oxide; Nuts and Bolts; Permeability; Post‐translational modifications; Prostaglandins; Protein kinase C; Proteins; Protein–protein interactions; Raf protein; Signal transduction; Signaling pathways; Therapeutic targets; Thrombosis; Vascular diseases; Signaling pathways; Post-translational modifications; Protein–protein interactions; Bradykinin storm
• ISSN: 1873-9601; 1873-961X
• DOI: 10.1007/s12079-021-00652-0

Bradykinin, a member of the kallikrein-kinin system (KKS), is associated with an inflammatory response pathway with diverse vascular permeability functions, including thrombosis and blood coagulation. In majority, bradykinin signals through Bradykinin Receptor B2 (B2R). B2R is a G protein-coupled receptor (GPCR) coupled to G protein family such as Gα
qs
, Gα
q
/Gα
11,
Gα
i1,
and Gβ1
γ
2
.
B2R stimulation leads to the activation of a signaling cascade of downstream molecules such as phospholipases, protein kinase C, Ras/Raf-1/MAPK, and PI3K/AKT and secondary messengers such as inositol-1,4,5-trisphosphate, diacylglycerol and Ca
2+
ions. These secondary messengers modulate the production of nitric oxide or prostaglandins. Bradykinin-mediated signaling is implicated in inflammation, chronic pain, vasculopathy, neuropathy, obesity, diabetes, and cancer. Despite the biomedical importance of bradykinin, a resource of bradykinin-mediated signaling pathway is currently not available. Here, we developed a pathway resource of signaling events mediated by bradykinin. By employing data mining strategies in the published literature, we describe an integrated pathway reaction map of bradykinin consisting of 233 reactions. Bradykinin signaling pathway events included 25 enzyme catalysis reactions, 12 translocations, 83 activation/inhibition reactions, 11 molecular associations, 45 protein expression and 57 gene regulation events. The pathway map is made publicly available on the WikiPathways Database with the ID URL:
https://www.wikipathways.org/index.php/Pathway:WP5132
. The bradykinin-mediated signaling pathway map will facilitate the identification of novel candidates as therapeutic targets for diseases associated with dysregulated bradykinin signaling.