title: Post-translational regulation of COX2 activity by FYN in prostate cancer cells.
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.
authors: Division of Nephrology and Kidney Disease Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors: Anna
authors: A
authors: Alexanian
authors: Division of Nephrology and Kidney Disease Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors: Bradley
authors: B
authors: Miller
authors: Department of Biochemistry, Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors: Marla
authors: M
authors: Chesnik
authors: Department of Biochemistry, Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors: Shama
authors: S
authors: Mirza
authors: Division of Nephrology and Kidney Disease Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors: Andrey
authors: A
authors: Sorokin
mesh_terms: D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D008565:Membrane Proteins; D051546:Cyclooxygenase 2; D051076:Proto-Oncogene Proteins c-fyn