5-Lipoxygenase Activation by Mapkapk-2 and Erks
Part of the
Advances in Experimental Medicine and Biology
book series (AEMB, volume 525)
5-Lipoxygenase (5-LO) is the key enzyme in the biosynthesis of proinflammatory leukotrienes from arachidonic acid (AA) . Ca2+, phosphatidylcholine, ATP, and hydroperoxides stimulate the enzymatic activity of 5-LO in vitro . However, the mechanisms involved in the agonist-induced 5-LO activation in intact cells are less clear. Stimuli that cause an elevation of the intracellular Ca2+ levels activate 5-LO. Ca2+ binds 5-LO in vitro at the enzyme’s C2 domain , which is a prerequisite for association with membranes .
KeywordsArachidonic Acid Free Arachidonic Acid MAPK Inhibitor SB203580 Efficient Phosphorylation Exogenous Arachidonic Acid
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
1 Radmark O. The molecular biology and regulation of 5-lipoxygenase. Am J Respir Crit Care Med 2001; 161:S11–15.Google Scholar
2 Hammarberg T, Provost P, Persson B, Rådmark O. The N-terminal domain of 5-lipoxygenase binds calcium and mediates calcium stimulation of enzyme activity. J Biol Chem 2000; 275:38787–38793.PubMedCrossRefGoogle Scholar
3 Kulkarni S, Das S, Funk CD, Murray D, Cho W. A molecular basis of specific subcellular localization of the C2-like domain of 5-lipoxygenase. J Biol Chem 2002; 277:13167–13174.PubMedCrossRefGoogle Scholar
4 Werz O, Szellas D, Steinhilber D, Radmark O. Arachidonic acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by MAPKAP kinase-2. J Biol Chem 2002; 277:14793–14800.PubMedCrossRefGoogle Scholar
Werz O, Klemm J, Samuelsson B, Rådmark O. 5-Lipoxygenase is phosphorylated by p38 kinase dependent MAPKAP kinases. Proc. Natl. Acad. Sci. 2000; 97:5261–5266.PubMedCrossRefGoogle Scholar
Lepley RA, Muskardin DT, Fitzpatrick FA. Tyrosine kinase activity modulates catalysis and translocation of cellular 5-lipoxygenase. J Biol Chem 1996; 271:6179–6184.PubMedCrossRefGoogle Scholar
Werz O, Buerkert E, Samuelsson B, Rådmark O, Steinhilber D. Activation of 5-lipoxygenase by cell stress is calcium-independent in human polymorphonuclear leukocytes. Blood 2002; 99:1044–1052.PubMedCrossRefGoogle Scholar
© Springer Science+Business Media New York 2003