PMID- 10580119
OWN - NLM
STAT- MEDLINE
DCOM- 20000113
LR  - 20190621
IS  - 0014-5793 (Print)
IS  - 0014-5793 (Linking)
VI  - 462
IP  - 1-2
DP  - 1999 Nov 26
TI  - Anthrax lethal factor cleaves MKK3 in macrophages and inhibits the
      LPS/IFNgamma-induced release of NO and TNFalpha.
PG  - 199-204
AB  - The lethal toxin of Bacillus anthracis consists of two proteins, PA and LF, which
      together induce lethal effects in animals and cause macrophage lysis. LF is a
      zinc-endopeptidase which cleaves two mitogen-activated protein kinase kinases
      (MAPKKs), Mek1 and Mek2, within the cytosol. Here, we show that also MKK3,
      another dual-specificity kinase that phosphorylates and activates p38 MAP kinase,
      is cleaved by LF in macrophages. No direct correlation between LF-induced cell
      death and cleavage of these MAPKKs was found in macrophage cell lines and primary
      peritoneal cells exhibiting different sensitivity to LF. However, we present the 
      first evidence that sublytic doses of LF cleave Meks and cause a substantial
      reduction in the production of NO and tumour necrosis factor-alpha induced by
      lipopolysaccharide/interferon gamma. We suggest that this effect of LF is
      relevant during the first stages of B. anthracis infection, when a reduction of
      the inflammatory response would permit growth and diffusion of the bacterium.
FAU - Pellizzari, R
AU  - Pellizzari R
AD  - Centro CNR Biomembrane and Dipartimento di Scienze Biomediche, Universita di
      Padova, via Colombo 3, 35121, Padua, Italy.
FAU - Guidi-Rontani, C
AU  - Guidi-Rontani C
FAU - Vitale, G
AU  - Vitale G
FAU - Mock, M
AU  - Mock M
FAU - Montecucco, C
AU  - Montecucco C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - FEBS Lett
JT  - FEBS letters
JID - 0155157
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Bacterial Toxins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (anthrax toxin)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 2)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 3)
RN  - EC 2.7.12.2 (Map2k3 protein, mouse)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
SB  - IM
MH  - Animals
MH  - *Antigens, Bacterial
MH  - Bacillus anthracis/metabolism
MH  - Bacterial Toxins/metabolism/*toxicity
MH  - Cells, Cultured
MH  - Drug Interactions
MH  - Interferon-gamma/pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - MAP Kinase Kinase 2
MH  - MAP Kinase Kinase 3
MH  - Macrophage Activation/drug effects
MH  - Macrophages/*drug effects/enzymology/metabolism
MH  - Macrophages, Peritoneal/drug effects/enzymology
MH  - Mice
MH  - Mitogen-Activated Protein Kinase Kinases/*metabolism
MH  - Nitric Oxide/*metabolism
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 1999/12/02 00:00
MHDA- 1999/12/02 00:01
CRDT- 1999/12/02 00:00
PHST- 1999/12/02 00:00 [pubmed]
PHST- 1999/12/02 00:01 [medline]
PHST- 1999/12/02 00:00 [entrez]
AID - S0014-5793(99)01502-1 [pii]
AID - 10.1016/s0014-5793(99)01502-1 [doi]
PST - ppublish
SO  - FEBS Lett. 1999 Nov 26;462(1-2):199-204. doi: 10.1016/s0014-5793(99)01502-1.