Regulating leukotriene synthesis: the role of nuclear 5-lipoxygenase.
Leukotrienes are lipid messengers involved in autocrine and paracrine cellular signaling. They are synthesized from arachidonic acid by the 5-lipoxygenase pathway. Current models of this enzymatic pathway recognize that a key step in initiating leukotriene synthesis is the calcium-mediated movement of enzymes, including 5-lipoxygenase, to intracellular membranes. However, 5-lipoxygenase can be imported into or exported from the nucleus before calcium activation. As a result, its subcellular localization will affect its ability to be activated by calcium, as well as the membrane to which it binds and its interaction with other enzymes. This commentary focuses on the role of 5-lipoxygenase compartmentation in determining its regulation and, ultimately, leukotriene synthesis.
Brock
Thomas G
TG
Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA. brocko@umich.edu
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D015289:Leukotrienes / Q000096:biosynthesis*; D008954:Models, Biological; D019913:Nuclear Localization Signals / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D000094765:Glutathione Peroxidase GPX1; D000099190:MAP-Kinase-Activated Kinase 2
D000255:Adenosine Triphosphate; D001094:Arachidonate 5-Lipoxygenase; D016718:Arachidonic Acid; D002118:Calcium; D017868:Cyclic AMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D005979:Glutathione Peroxidase; D047908:Intracellular Signaling Peptides and Proteins; D015289:Leukotrienes; D019913:Nuclear Localization Signals; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D000094765:Glutathione Peroxidase GPX1; D000099190:MAP-Kinase-Activated Kinase 2