A member of the p38 mitogen-activated protein kinase family is responsible for transcriptional induction of Dopa decarboxylase in the epidermis of Drosophila melanogaster during the innate immune response.
Drosophila innate immunity is controlled primarily by the activation of IMD (immune deficiency) or Toll signaling leading to the production of antimicrobial peptides (AMPs). IMD signaling also activates the JUN N-terminal kinase (JNK) cascade, which is responsible for immune induction of non-antimicrobial peptide immune gene transcription though the transcription factor AP-1. Transcription of the Dopa decarboxylase (Ddc) gene is induced in response to gram-negative and gram-positive septic injury, but not aseptic wounding. Transcription is induced throughout the epidermis and not specifically at the site of infection. Ddc transcripts are detectible within 2 h and remain high for several hours following infection with either gram-negative or gram-positive bacteria. Using Ddc-green fluorescent protein (GFP) reporter gene constructs, we show that a conserved consensus AP-1 binding site upstream of the Ddc transcription start site is required for induction. However, neither the Toll, IMD, nor JNK pathway is involved. Rather, Ddc transcription depends on a previously uncharacterized member of the p38 mitogen-activated protein kinase family, p38c. We propose that the involvement of DDC in a new pathway involved in Drosophila immunity increases the levels of dopamine, which is metabolized to produce reactive quinones that exert an antimicrobial effect on invading bacteria.
Davis
Monica M
MM
Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada.
Primrose
David A
DA
Hodgetts
Ross B
RB
D000595:Amino Acid Sequence; D000818:Animals; D001424:Bacterial Infections / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D001665:Binding Sites; D017124:Conserved Sequence; D004296:Dopa Decarboxylase / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D004790:Enzyme Induction; D004817:Epidermis / Q000201:enzymology* / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008969:Molecular Sequence Data; D011485:Protein Binding; D016019:Survival Analysis; D013997:Time Factors; D051193:Toll-Like Receptors / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D029721:Drosophila Proteins; D051193:Toll-Like Receptors; D018808:Transcription Factor AP-1; C439909:imd protein, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D004296:Dopa Decarboxylase