P38 mapks regulate the expression of genes in the dopamine synthesis pathway through phosphorylation of NR4A nuclear receptors

Yusuke Sekine, Shuichi Takagahara, Ryo Hatanaka, Takeshi Watanabe, Haruka Oguchi, Takuya Noguchi, Isao Naguro, Kazuto Kobayashi, Makoto Tsunoda, Takashi Funatsu, Hiroshi Nomura, Takeshi Toyoda, Norio Matsuki, Erina Kuranaga, Masayuki Miura, Kohsuke Takeda, Hidenori Ichijo

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)


In Drosophila, the melanization reaction is an important defense mechanism against injury and invasion of microorganisms. Drosophila tyrosine hydroxylase (TH, also known as Pale) and dopa decarboxylase (Ddc), key enzymes in the dopamine synthesis pathway, underlie the melanin synthesis by providing the melanin precursors dopa and dopamine, respectively. It has been shown that expression of Drosophila TH and Ddc is induced in various physiological and pathological conditions, including bacterial challenge; however, the mechanism involved has not been fully elucidated. Here, we show that ectopic activation of p38 MAPK induces TH and Ddc expression, leading to upregulation of melanization in the Drosophila cuticle. This p38-dependent melanization was attenuated by knockdown of TH and Ddc, as well as by that of Drosophila HR38, a member of the NR4A family of nuclear receptors. In mammalian cells, p38 phosphorylated mammalian NR4As and Drosophila HR38 and potentiated these NR4As to transactivate a promoter containing NR4Abinding elements, with this transactivation being, at least in part, dependent on the phosphorylation. This suggests an evolutionarily conserved role for p38 MAPKs in the regulation of NR4As. Thus, p38-regulated gene induction through NR4As appears to function in the dopamine synthesis pathway and may be involved in immune and stress responses.

Original languageEnglish
Pages (from-to)3006-3016
Number of pages11
JournalJournal of cell science
Issue number17
Publication statusPublished - 2011 Sep 1
Externally publishedYes


  • NR4A nuclear receptor
  • P38 mapk
  • Stress response
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Cell Biology


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