title: Protein kinases in organ ischemia and reperfusion.
abstract: There is ample evidence of the role that protein kinases play in the signaling pathways secondary to ischemia and reperfusion (I/R). The protein kinases initiate several interconnected downstream cascades regulated by phosphorylation and dephosphorylation reactions. The signaling transduction pathways ultimately initiate the nuclear transcription of the inflammatory and anti-inflammatory genes to repair and assist in the recovery of damaged cells. Although some of the I/R mechanisms are well identified, there is still a lack of general application of this knowledge in clinical practice and particularly in the role that their induction or inhibition can play in disease treatment or improving illness management. This is a review of the current understanding of the role that protein kinases play in the phosphoregulatory mechanisms, which mediate the complex processes of signal transduction secondary to organ I/R injury. Under ischemic conditions, diverse families of protein kinases, including tyrosine kinases, receptor serine kinases, and mitogen-activated protein (MAP) kinases, catalyze the phosphorylation of several proteins that initiate the cascade of events regulated by phosphorylation reactions and subsequent inflammatory gene expression. This phosphorylation catalyzed by protein kinases can nevertheless be reversed by a second group of enzymes, called protein phosphatases, which remove the phosphate and in that way modulate the activity of the protein kinases. The potential role that protein kinase inhibitors play is discussed on the basis of a new understanding of the mechanisms modulating phosphoregulated pathways.
authors.affiliation: Department of Research and Surgery, Michigan State University/KCMS, Kalamazoo, Michigan 49008, USA. toledo@kcms.msu.edu
authors.forename: Luis H
authors.initials: LH
authors.lastname: Toledo-Pereyra
authors.forename: Fernando
authors.initials: F
authors.lastname: Lopez-Neblina
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Toledo
mesh_terms: D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006801:Humans; D011494:Protein Kinases / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D015427:Reperfusion Injury / Q000201:enzymology* / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology; D013379:Substrate Specificity; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
chemical_list: D011494:Protein Kinases; D020794:Receptor Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases