Alexanian Anna, Miller Bradley, Chesnik Marla, Mirza Shama, Sorokin Andrey
Division of Nephrology and Kidney Disease Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Department of Biochemistry, Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Oncotarget. 2014 Jun 30;5(12):4232-43. doi: 10.18632/oncotarget.1983.
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.
虽然在人类癌症中COX2表达增加且前列腺素水平升高，但COX2在翻译后水平的调控机制尚不清楚。最初观察到COX2与非受体酪氨酸激酶FYN形成加合物，促使我们研究FYN介导的COX2翻译后调控。我们发现FYN增加了前列腺癌细胞DU145中COX2的活性，这与COX2或COX1蛋白表达水平的变化无关。我们报告FYN使人类COX2的Tyr 446位点磷酸化，虽然相应的磷酸模拟COX2突变促进了COX2的活性，但磷酸化阻断突变阻止了FYN介导的COX2活性增加。
