Protein kinase A inhibits leukotriene synthesis by phosphorylation of 5-lipoxygenase on serine 523

M Luo, SM Jones, SM Phare, MJ Coffey… - Journal of Biological …, 2004 - ASBMB
Leukotrienes (LTs) are lipid messengers generated by leukocytes that drive inflammation
and modulate neighboring cell function. The synthesis of LTs from arachidonic acid is
initiated by the enzyme 5-lipoxygenase (5-LO). We report for the first time that LT synthesis is
inhibited by the direct action of protein kinase A (PKA) on 5-LO. The catalytic subunit of PKA
directly phosphorylated 5-LO in vivo and in vitro and inhibited activity in intact cells and in
vitro. Mutation of Ser-523 on human 5-LO prevented phosphorylation by PKA and restored …