Post-translational regulation of COX2 activity by FYN in prostate cancer cells

// Anna Alexanian 1 , Bradley Miller 1 , Marla Chesnik 2 , Shama Mirza 2 and Andrey Sorokin 1 1 Division of Nephrology and Kidney Disease Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA, 2 Department of Biochemistry, Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA Correspondence: Andrey Sorokin, email: // Keywords : COX2 regulation/DU145 cells/prostaglandins/phosphorylation/prostate cancer/Src family kinases Received : March 7, 2014 Accepted : May 16, 2014 Published : May 18, 2014 Abstract While increased COX2 expression and prostaglandin levels are elevated in human cancers, the mechanisms of COX2 regulation at the post-translational level are unknown. Initial observation that COX2 forms adduct with non-receptor tyrosine kinase FYN, prompted us to study FYN-mediated post-translational regulation of COX2. We found that FYN increased COX2 activity in prostate cancer cells DU145, independent of changes in COX2 or COX1 protein expression levels. We report that FYN phosphorylates human COX2 on Tyr 446, and while corresponding phospho-mimetic COX2 mutation promotes COX2 activity, the phosphorylation blocking mutation prevents FYN-mediated increase in COX2 activity.