A Rho exchange factor mediates fMet-Leu-Phe-induced NF-kappaB activation in human peripheral blood monocytes.
We reported previously that fMLP stimulates NF-kappaB activation, and this function of fMLP requires small GTPase RhoA in human peripheral blood monocytes (Huang, S., Chen, L.-Y., Zuraw, B. L., Ye, R. D., and Pan, Z. K. (2001) J. Biol. Chem. 276, 40977-40981). Here we present evidence that RhoA associates specifically with the guanine nucleotide exchange factor Lbc in human peripheral blood monocytes stimulated with fMLP and that Lbc specifically catalyzes the guanine nucleotide exchange activity of RhoA in human peripheral blood monocytes. Cotransfection of the monocytic THP1 cells with lbc with a kappaB promoter reporter plasmid results in a marked increase in NF-kappaB-mediated reporter gene expression. Finally, Lbc-enhanced NF-kappaB activation is inhibited by a RhoA inhibitor, C3 transferase from Clostridium botulinum. A dominant-negative form of RhoA (T19N) also inhibited Lbc-enhanced reporter gene expression in a kappaB-dependent manner. These results indicate that guanine nucleotide exchange factor Lbc is a novel signal transducer for RhoA-mediated NF-kappaB activation in human peripheral blood monocytes stimulated with bacterial products.
Chen
Ling-Yu
LY
Department of Microbiology and Immunology, Medical College of Ohio, Toledo, Ohio 43614, USA.
Zuraw
Bruce L
BL
Ye
Richard D
RD
Pan
Zhixing K
ZK
D054758:A Kinase Anchor Proteins; D036002:ADP Ribose Transferases / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D001905:Botulinum Toxins / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000737:chemistry; D005799:Genes, Dominant; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000737:chemistry / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D015151:Immunoblotting; D007962:Leukocytes / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D009000:Monocytes / Q000378:metabolism*; D009154:Mutation; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000737:chemistry / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000502:physiology*; D012234:Rho Factor / Q000737:chemistry* / Q000502:physiology; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
D054758:A Kinase Anchor Proteins; C085467:AKAP13 protein, human; D048868:Adaptor Proteins, Signal Transducing; D020662:Guanine Nucleotide Exchange Factors; D015778:Minor Histocompatibility Antigens; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D012234:Rho Factor; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009240:N-Formylmethionine Leucyl-Phenylalanine; D008156:Luciferases; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D037342:Pertussis Toxin; D001905:Botulinum Toxins; D019204:GTP-Binding Proteins