5-lipoxygenase phosphorylation

Menard C., Valastro B., Martel M. A., Chartier T., Marineau A., Baudry M., and Massicotte G. (2005). AMPA receptor phosphorylation is selectively regulated by constitutive phospholipase A2 and 5-lipoxygenase activities. Hippocampus 15 370-380. 

In 1991 inhibition of PKC activity was found to be at the basis of the vascular smooth muscle cell growth arrest induced by a-tocopherol [16,17]. A number of reports have subsequently confirmed the involvement of PKC in the effect of a-tocopherol on different cell types, including monocytes, macrophages, neutrophils, fibroblasts and mesangial cells [8,18-20]. a-Tocopherol, but not P-tocopherol, was found to inhibit thrombin-induced PKC activation and endothelin secretion in endothelial cells [21]. a-Tocopherol, and not P-tocopherol or trolox, inhibits the activity of PKC fi-om monocytes, followed by inhibition of phosphorylation and translocation of the cytosolic factor p47(phox) and by an impaired assembly of the NADPH-oxidase and of superoxide production [22]. a-Tocopherol has the important biological effect of inhibiting the release of the proinflammatory cytokine, IL-lp, via inhibition of the 5-lipoxygenase pathway [23]. 

Lipoxygenase (5LO) is upregulated in AD, and plays an active role in the development of brain amyloidosis in the APP transgenic mice. APP transgenic mice treated with Zileuton, a specific 5LO inhibitor, showed memory improvement reduction of Ap levels and deposition, secondary to a downregulation of the y-secretase pathway. Zileuton-treated mice had a reduction in tau phosphorylation, secondary to a decreased activation ofthe cdk5 kinase [558],... 

Moduiation of enzymatic activity Protein kinase C (PKC) " Protein kinase B (PKB) " Protein tyrosine phosphorylation Protein phosphatase 2A (PP2A) " Phospholipase A2 " " Cyclooxygenase 5-Lipoxygenase Glutathione S-transferase NADPH-oxidase ... 

Luo, M., S. M. Jones et al. 2004. Protein kinase A inhibits leukotriene synthesis by phosphorylation of 5-lipoxygenase on serine 523. J Biol Chem 279(40) 41512-41520. 

Werz, O., E. Burkert et al. 2002. Extracellular signal-regulated kinases phosphorylate 5-lipoxygenase and stimulate 5-lipoxygenase product formation in leukocytes. FASEBJ 16(11) 1441-1443. 

Werz, O., D. Szellas et al. 2002. Arachidonie acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by MAPK-activated protein kinase 2 (MK2). 277(17) 14793-14800. 

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