Mechanisms of regulation of the MacMARCKS gene in macrophages by bacterial lipopolysaccharide.
Bacterial lipopolysaccharide (LPS) stably induced the protein kinase C substrate, MacMARCKS, in murine resident peritoneal macrophages; initial induction of MacMARCKS mRNA was detected within 15 min and was protein synthesis-independent. This response was observed in the macrophage cell line RAW264, and occurred also in response to plasmid DNA, a partial mimetic of other responses to LPS. In murine bone marrow-derived macrophages, MacMARCKS was expressed constitutively due to induction by macrophage colony-stimulating factor. Nuclear run-on transcription revealed that, like tumor necrosis factor alpha (TNF-alpha), MacMARCKS was transcribed constitutively in RAW264 cells. The MacMARCKS promoter was sequenced to -1.7 kb and the transcription start site determined. Transient transfections of RAW264 cells revealed that the 113-bp GC-rich proximal promoter contained all the elements required for both high basal activity and 15- to 20-fold activation by LPS.
Chang
S
S
Department of Biochemistry, Centre for Molecular and Cellular Biology, University of Queensland, Australia.
Stacey
K J
KJ
Chen
J
J
Costelloe
E O
EO
Aderem
A
A
Hume
D A
DA
D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002148:Calmodulin-Binding Proteins; D005786:Gene Expression Regulation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D002148:Calmodulin-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; C512945:Marcksl1 protein, mouse; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D011493:Protein Kinase C