TY - JOUR
T1 - P38 mapks regulate the expression of genes in the dopamine synthesis pathway through phosphorylation of NR4A nuclear receptors
AU - Sekine, Yusuke
AU - Takagahara, Shuichi
AU - Hatanaka, Ryo
AU - Watanabe, Takeshi
AU - Oguchi, Haruka
AU - Noguchi, Takuya
AU - Naguro, Isao
AU - Kobayashi, Kazuto
AU - Tsunoda, Makoto
AU - Funatsu, Takashi
AU - Nomura, Hiroshi
AU - Toyoda, Takeshi
AU - Matsuki, Norio
AU - Kuranaga, Erina
AU - Miura, Masayuki
AU - Takeda, Kohsuke
AU - Ichijo, Hidenori
PY - 2011/9/1
Y1 - 2011/9/1
N2 - 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.
AB - 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.
KW - NR4A nuclear receptor
KW - P38 mapk
KW - Stress response
KW - Tyrosine hydroxylase
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U2 - 10.1242/jcs.085902
DO - 10.1242/jcs.085902
M3 - Article
C2 - 21878507
AN - SCOPUS:80054050110
VL - 124
SP - 3006
EP - 3016
JO - The Quarterly journal of microscopical science
JF - The Quarterly journal of microscopical science
SN - 0021-9533
IS - 17
ER -