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

Anna Alexanian1, Bradley Miller1, Marla Chesnik2

  • 1Division of Nephrology and Kidney Disease Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Oncotarget
|June 28, 2014
PubMed

Insights

FYN kinase phosphorylates COX2 at Tyr 446, increasing its activity in prostate cancer cells. This FYN-mediated phosphorylation enhances cyclooxygenase-2 (COX2) activity, independent of protein levels.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Biochemistry

Background:

  • Elevated cyclooxygenase-2 (COX2) expression and prostaglandin levels are hallmarks of human cancers.
  • Mechanisms regulating COX2 at the post-translational level remain largely unknown.
  • Cyclooxygenase-2 (COX2) has been observed to form adducts with the non-receptor tyrosine kinase FYN.

Purpose of the Study:

  • To investigate the role of FYN-mediated post-translational regulation of COX2.
  • To determine if FYN affects COX2 activity in prostate cancer cells.

Main Methods:

  • Utilized DU145 prostate cancer cells to study FYN-mediated COX2 regulation.
  • Assessed COX2 activity in response to FYN interaction.
  • Investigated FYN-mediated phosphorylation of human COX2 at Tyr 446 using phospho-mimetic and phosphorylation-blocking mutations.

Main Results:

  • FYN significantly increased COX2 activity in DU145 prostate cancer cells.
  • This increase in COX2 activity was independent of changes in COX2 or COX1 protein expression levels.
  • FYN was found to phosphorylate human COX2 on Tyr 446.

Conclusions:

  • FYN-mediated phosphorylation of COX2 at Tyr 446 is a key mechanism for increasing COX2 activity.
  • Phosphorylation of COX2 by FYN enhances its enzymatic activity, potentially contributing to cancer progression.
  • Targeting the FYN-COX2 interaction may offer novel therapeutic strategies in cancers with elevated COX2.

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