Regulating leukotriene synthesis: The role of nuclear 5‐lipoxygenase

  title={Regulating leukotriene synthesis: The role of nuclear 5‐lipoxygenase},
  author={Thomas G. Brock},
  journal={Journal of Cellular Biochemistry},
  • T. Brock
  • Published 15 December 2005
  • Biology
  • Journal of Cellular Biochemistry
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… 
Lysophospholipid acyltransferases and leukotriene biosynthesis: intersection of the Lands cycle and the arachidonate PI cycle[S]
Leukotrienes (LTs) are autacoids derived from the precursor arachidonic acid (AA) via the action of five-lipoxygenase (5-LO) that are mediated by the disappearance of free AA from the nuclear membrane, transfer to the ER for Lands cycle reesterification into PI, and population of PI for cell membrane signaling.
Studies on coactosin-like protein interaction with 5-lipoxygenase
The aim of present thesis was to investigate the effects of a small Coactosin-like Protein (CLP) on the 5-LO activation and stability in order to define the potential role of CLP in mechanisms involved in formation of LTs, and found that CLP can function as a scaffold for 5- LO similar to membranes.
The enzymatic machinery of leukotriene biosynthesis : Studies on ontogenic expression, interactions and function
Evidence is reported that production of LTs can occur in cells of the fetal and adult hematopoietic compartments and that deficiency of the FLAP gene (and leukotrienes) may affect lymphocyte maturation.
Biosynthesis and metabolism of leukotrienes.
These metabolic transformations of the primary leukotrienes are critical for termination of their biological activity, and defects in expression of participating enzymes may be involved in specific genetic disease.
Phosphorylation of Serine 271 on 5-Lipoxygenase and Its Role in Nuclear Export*
Results indicate that the phosphorylation of Ser-271 serves to inhibit the nuclear export of 5-LO, which works in concert with nuclear import, which is regulated by phosphorylated on Ser-523, to determine the subcellular distribution of 3T3, which in turn regulates leukotriene biosynthesis.
Cross-Talk between Cancer Cells and the Tumour Microenvironment: The Role of the 5-Lipoxygenase Pathway
Potential routes through which cancer cells may utilise the 5-lipoxygenase pathway to interact with the tumour microenvironment during the development and progression of a tumour are discussed.


Nuclear localization of 5-lipoxygenase as a determinant of leukotriene B4 synthetic capacity
It is unequivocally demonstrate that the positioning of 5-LO within the nucleus of resting cells is a powerful determinant of the capacity to generate LTB4 upon subsequent activation.
Protein Kinase A Inhibits Leukotriene Synthesis by Phosphorylation of 5-Lipoxygenase on Serine 523*
Results indicate that PKA phosphorylates 5-LO on Ser-523, which inhibits the catalytic activity of 5- LO and reduces cellular LT generation, which may be important in limiting inflammation and maintaining homeostasis.
Translocation and Leukotriene Synthetic Capacity of Nuclear 5-Lipoxygenase in Rat Basophilic Leukemia Cells and Alveolar Macrophages (*)
By virtue of its enzymatic activity and ability to translocate, nuclear 5-LO has the potential to contribute to LT synthesis in RBL cells and AMs and provides a foundation for considering the individual functions of discrete pools of 5- LO in future studies.
Redistribution of 5-lipoxygenase and cytosolic phospholipase A2 to the nuclear fraction upon macrophage activation.
Data demonstrate for the first time coordinate subcellular localization of the key proteins involved in leukotriene synthesis from endogenous arachidonate.
Localization of 5-lipoxygenase to the nucleus of unstimulated rat basophilic leukemia cells.
The finding that a substantial proportion of enzyme is localized within the nucleus of unstimulated RBL cells suggests potentially novel roles for 5-LO or its products within the nuclei.
Determinants of 5-Lipoxygenase Nuclear Localization Using Green Fluorescent Protein/5-Lipoxygenase Fusion Proteins*
The combined data suggest that 5-lipoxygenase enters the nucleus not by a classical nuclear localization signal but by a non-conventional signal located in the predicted β-barrel domain that may be masked by structural alterations.
Extracellular signal‐regulated kinases phosphorylate 5lipoxygenase and stimulate 5‐lipoxygenase product formation in leukocytes
It is demonstrated that extracellular signal‐regulated kinases (ERKs) can phosphorylate 5‐LO in vitro and the data suggest that ERKs and p38 MAPK‐regulated MAPKAPKs can act in conjunction to stimulate 5‐ LO by phosphorylation.
5-lipoxygenase and 5-lipoxygenase-activating protein are localized in the nuclear envelope of activated human leukocytes
The nuclear envelope is the intracellular site at which 5- LO and FLAP act to metabolize arachidonic acid, and that ionophore activation of neutrophils and monocytes results in the translocation of 5-LO from a nonsedimentable location to the nuclear envelope.
The involvement of extracellular calcium in the formation of 5-lipoxygenase metabolites by human polymorphonuclear leukocytes.
The data indicate that the Ca2+ requirement of phospholipase A2 can only be met by an additional influx of extracellular calcium, whereas 5-lipoxygenase will operate already at levels provided by intracellular stores.