RRC ID 15568
Author Sekine Y, Takagahara S, Hatanaka R, Watanabe T, Oguchi H, Noguchi T, Naguro I, Kobayashi K, Tsunoda M, Funatsu T, Nomura H, Toyoda T, Matsuki N, Kuranaga E, Miura M, Takeda K, Ichijo H.
Title p38 MAPKs regulate the expression of genes in the dopamine synthesis pathway through phosphorylation of NR4A nuclear receptors.
Journal J Cell Sci
Abstract 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 NR4A-binding 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.
Volume 124(Pt 17)
Pages 3006-16
Published 2011-9-1
DOI 10.1242/jcs.085902
PII 124/17/3006
PMID 21878507
MeSH Amino Acid Sequence Animals Dopa Decarboxylase / biosynthesis* Dopa Decarboxylase / genetics Dopa Decarboxylase / metabolism Dopamine / biosynthesis* Drosophila Female Gene Expression Regulation* Male Molecular Sequence Data Phosphorylation Receptors, Cytoplasmic and Nuclear / biosynthesis Receptors, Cytoplasmic and Nuclear / genetics Receptors, Cytoplasmic and Nuclear / metabolism* Sequence Alignment Transfection p38 Mitogen-Activated Protein Kinases / genetics* p38 Mitogen-Activated Protein Kinases / metabolism*
IF 4.573
Times Cited 18
Drosophila 5475R-2 7393R-1 4153R-2 9738R-1 10697R-1 DGRC#109839 DGRC#109845 DGRC#109846