Post-translational regulation of COX2 activity by FYN in prostate cancer cells.
Post-translational regulation of COX2 activity by FYN in prostate cancer cells.
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DOI：
10.18632/oncotarget.1983
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发表时间：
2014-06-30
期刊：
影响因子：
--
通讯作者：
Sorokin A
中科院分区：
文献类型：
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作者：
Alexanian A;Miller B;Chesnik M;Mirza S;Sorokin A
虽然COX2表达增加和前列腺素水平在人类癌症中升高，但COX2在翻译后水平的调节机制尚不清楚。初步观察到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，与COX2或COX1蛋白表达水平的变化无关。我们报道了FYN在Tyr 446上磷酸化人类COX2，虽然相应的模拟磷酸化的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活性的增加。
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.