Phosphorylation and Activation of 5-Lipoxygenase by P38 Kinase-Activated MAPKAP Kinases

Abstract

5-lipoxygenase (5-LO) catalyzes the formation of leukotriene A₄ from arachidonic acid. Factors determining 5-LO enzyme activity are calcium, phosphatidylcholine (membranes), ATP, and the cellular redox status. Also, a possible role of phosporylation events for 5-LO activity in the cell has been discussed. In particular, connection to the activity of protein kinase C in alveolar macrophages [1] and the effects of protein tyrosine kinase inhibitors in HL-60 cells and polymorphonuclear leukocytes (PMNL) [2] indicated such a role. The three MAP kinase families, the extracellular regulated kinases (ERKs), the c-jun N-terminal kinases/stress activated protein kinases (JNKs/SAPKs), and the p38 MAP kinases, have been implicated in a variety of cellular functions, including cell proliferation, differentiation, and immune responses [3, 4]. The ERKs are activated mainly by mitogens such as growth factors and G-protein coupled receptor agonists, while JNKs and p38 are activated by various types of cellular stress.