Intracellular kinases in inflammatory signaling pathways

Intracellular kinases in inflammatory signaling pathways are a broad class of enzymes that relay signals from cell-surface receptors, such as cytokine and Toll-like receptors, to the nucleus to regulate the immune response [1.2.1, 1.4.2]. Key families include the Janus kinases (JAKs), mitogen-activated protein kinases (MAPKs), and the IkappaB kinase (IKK) complex, which facilitate the activation of transcription factors like STAT and NF-kappaB [1.2.1, 1.4.4]. Other important members include spleen tyrosine kinase (Syk), Bruton's tyrosine kinase (BTK), and interleukin-1 receptor-associated kinases (IRAKs) [1.2.1, 1.3.5]. These kinases are essential for the production of pro-inflammatory cytokines and the coordination of cellular processes like proliferation and apoptosis [1.1.3, 1.2.2]. Dysregulation of these signaling cascades is central to the pathogenesis of autoimmune and chronic inflammatory diseases, including rheumatoid arthritis, psoriasis, and inflammatory bowel disease [1.2.1, 1.3.2]. Therapeutic targeting of these kinases with small-molecule inhibitors, such as tofacitinib and baricitinib, has revolutionized the treatment of these conditions by providing oral alternatives to biologic therapies [1.3.1, 1.3.4]. However, because these kinases often participate in multiple homeostatic pathways, their inhibition can lead to significant safety concerns, including increased susceptibility to infections, venous thromboembolism, and cardiovascular events [1.3.1, 1.3.4].

Other names

Signaling kinases in inflammationPro-inflammatory kinasesIntracellular signaling molecules in inflammationCytokine signaling kinases

Inhibition of intracellular phosphorylation cascades, such as the JAK-STAT or MAPK pathways, to block the transmission of pro-inflammatory signals from cell-surface receptors to the nucleus, thereby preventing the transcription of inflammatory genes.