Protein kinase cascades activated by stress and inflammatory cytokines

摘要: Signal transduction pathways constructed around a core module of three consecutive protein kinases, the most distal being member extracellular signal-regulated kinase (ERK) family, are ubiquitous among eukaryotes. Recent work has defined two cascades activated preferentially by inflammatory cytokines TNF-α and IL-1-β, as well wide variety cellular stresses such UV ionizing radiation, hyperosmolarity, heat stress, oxidative etc. One pathway converges on ERK subfamily known ‘stress activated’ kinases (SAPKs, also termed Jun N-terminal JNKs), whereas second recruits p38 kinases. Upstream inputs diverse, include small GTPases (primarily Rac Cdc42; secondarily Ras) acting through mammalian homologs yeast Ste20 kinase, other subfamilies (e.g. GC kinase) ceramide, putative messenger for certain actions. These signal cell cycle delay, repair or apoptosis in cells, activation immune reticuloendothelial cells.