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Aromatase is phosphorylated in situ at serine-118.

Miller, Todd W and Shin, Incheol and Kagawa, Norio and Evans, Dean Brent and Waterman, Michael R and Arteaga, Carlos L (2008) Aromatase is phosphorylated in situ at serine-118. The Journal of Steroid Biochemistry and Molecular Biology, 112 (1-3). pp. 95-101. ISSN 0960-0760

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.

Item Type: Article
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Additional Information: author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords: Aromatase; Phosphorylation; Estrogen synthase; Post-translational modification
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Date Deposited: 14 Dec 2009 13:48
Last Modified: 14 Dec 2009 13:48
URI: https://oak.novartis.com/id/eprint/1357

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