title: Role of mitogen- and stress-activated kinases in ischemic injury.
abstract: Protein kinase-mediated signaling cascades constitute the major route by which cells respond to their extracellular environment. Of these, three well-characterized mitogen-activated protein kinase (MAPK) signaling pathways are those that use the extracellular signal-regulated kinase (ERK1/2) or the stress-activated protein kinase (p38/SAPK2 or JNK/SAPK) pathways. Mitogenic stimulation of the MAPK-ERK1/2 pathway modulates the activity of many transcription factors, leading to biological responses such as proliferation and differentiation. In contrast, the p38/SAPK2 and JNK/SAPK (c-Jun amino-terminal kinase/stress-activated protein kinase) pathways are only weakly, if at all, activated by mitogens, but are strongly activated by stress stimuli. There is now a growing body of evidence showing that these kinase signaling pathways become activated following a variety of injury stimuli including focal cerebral ischemia. Whether their activation, however, is merely an epiphenomenon of the process of cell death, or is actually involved in the mechanisms underlying ischemia-induced degeneration, remains to be fully understood. This review provides an overview of the current understanding of kinase pathway activation following cerebral ischemia and discusses the evidence supporting a role for these kinases in the mechanisms underlying ischemia-induced cell death.
authors.affiliation: Neurology CEDD, GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, UK. Elaine_A_Irving@gsk.com
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Irving
authors.forename: Mark
authors.initials: M
authors.lastname: Bamford
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000201:enzymology; D006801:Humans; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism
chemical_list: D020928:Mitogen-Activated Protein Kinases