Aromatase is phosphorylated in situ at serine-118

Todd W. Miller, Incheol Shin, Norio Kagawa, Dean B. Evans, Michael R. Waterman, Carlos L. Arteaga

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Phosphorylation of the cytochrome P450 aromatase has been proposed as a switch to rapidly modulate enzymatic activity and estrogen biosynthesis. Herein, we demonstrate that aromatase serine-118 is a potential phosphorylation site in mammalian cells. The amino acid context surrounding S118 is highly conserved among diverse animal species and suggests that an AGC-like kinase may phosphorylate aromatase. Mutation of S118 to Ala blocked phosphorylation. Mutation of S118 to either Ala or Asp destabilized aromatase, indicating an important structural role for S118. The phosphomimetic S118D mutant showed decreased specific enzymatic activity, decreased Vmax, and increased Km, while the S118A phospho-inhibiting mutant showed opposite effects. Our findings suggest that phosphorylation of S118 may decrease aromatase activity, presenting a mechanism whereby kinase signaling may modulate estrogen production and hormone balance.

Original languageEnglish (US)
Pages (from-to)95-101
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume112
Issue number1-3
DOIs
Publication statusPublished - Nov 1 2008

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Keywords

  • Aromatase
  • Estrogen synthase
  • Phosphorylation
  • Post-translational modification

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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