Lipopolysaccharide induces phosphorylation of MAD3 and activation of c-Rel and related NF-kappa B proteins in human monocytic THP-1 cells.

Cordle SR, Donald R, Read MA, Hawiger J
J Biol Chem. 1993 268 (16): 11803-10

PMID: 8505309

Many effects of lipopolysaccharide (LPS) on gene expression, including that of human immunodeficiency virus (HIV), in monocytic cells are mediated by activation of kappa B DNA-binding proteins. However, the specific members of the NF-kappa B/Rel transcription factor family involved in the LPS response, and the mechanisms through which LPS-generated signals are transduced remain unclear. Here we show that LPS induces nuclear expression of c-Rel/p50 heterodimers as well as p50/p65 (NF-kappa B) kappa B DNA-binding complexes in human monocytic THP-1 cells. Nuclear localization of these proteins occurred concomitantly with a rapid decrease in their cytosolic levels and was independent of phorbol ester-sensitive protein kinase C. Within 24 h following LPS stimulation there was a striking increase in the levels of c-Rel, p105, and p50 in the cytosol. The increased levels of these proteins correlated with increases in the amounts of their mRNAs during LPS activation of THP-1 cells. LPS activation of THP-1 cells resulted in phosphorylation of MAD3 (an I kappa B-like protein), a rapid increase in MAD3 mRNA, and an increase in MAD3 protein by 2 h. Thus, LPS activation of human monocytic cells results in nuclear expression of c-Rel/p50 and p50/p65 (NF-kappa B) and induces phosphorylation of MAD3.

MeSH Terms (27)

Amino Acid Sequence Antibodies Base Sequence Blotting, Western Cell Line DNA-Binding Proteins Enhancer Elements, Genetic HIV Long Terminal Repeat Humans I-kappa B Proteins Immunoglobulin kappa-Chains Leukemia, Monocytic, Acute Lipopolysaccharides Molecular Sequence Data Monocytes NF-kappa B NF-KappaB Inhibitor alpha Oligodeoxyribonucleotides Peptides Phosphorylation Protein-Tyrosine Kinases Proto-Oncogene Proteins Proto-Oncogene Proteins c-rel Proto-Oncogenes RNA, Messenger Tetradecanoylphorbol Acetate Transcription, Genetic

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