Protein kinase involved in inflammatory signaling

Protein kinases involved in inflammatory signaling are a broad class of enzymes that regulate the cellular response to pro-inflammatory stimuli by phosphorylating specific protein substrates (Source: PubMed, PMID: 28844937). This group includes several critical families such as Janus kinases (JAKs), Mitogen-activated protein kinases (MAPKs), IkappaB kinases (IKKs), and Spleen tyrosine kinase (SYK), which mediate signals from cytokine receptors and Toll-like receptors (Source: Nature Reviews Drug Discovery, doi:10.1038/nrd.2017.133). Upon activation, these kinases trigger downstream cascades that culminate in the activation of transcription factors like NF-kappaB and STAT, leading to the expression of inflammatory mediators (Source: NIH, StatPearls). Dysregulation of these pathways is central to the pathogenesis of various autoimmune and chronic inflammatory conditions, such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease (Source: Journal of Inflammation Research, doi:10.2147/JIR.S251350). Therapeutic targeting of these kinases with small-molecule inhibitors has revolutionized the treatment of these diseases by blocking the intracellular transmission of inflammatory signals (Source: Lancet, doi:10.1016/S0140-6736(21)00685-3). However, because these kinases often play roles in normal immune surveillance and hematopoiesis, their inhibition can lead to side effects such as immunosuppression and cytopenias (Source: FDA, Drug Safety Communications).

Other names

Inflammatory kinasePro-inflammatory kinaseKinase in immune signalingCytokine-signaling kinaseInflammatory signaling kinase

Small-molecule inhibitors typically bind to the ATP-binding pocket of the kinase domain, preventing the transfer of a phosphate group to the substrate and thereby interrupting the inflammatory signaling cascade (Source: PubChem; PubMed, PMID: 30107174).