Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Biochem Biophys Res Commun. 1998 Jul 30;248(3):706-11.

Anthrax lethal factor cleaves the N-terminus of MAPKKs and induces tyrosine/threonine phosphorylation of MAPKs in cultured macrophages.

Author information

  • 1Dipartimento di Scienze Biomediche, Universit√† di Padova, Italy.

Abstract

Lethal factor (LF) is the major virulence factor produced by Bacillus anthracis. LF is sufficient to cause death in laboratory animals and cytolysis of peritoneal macrophages and macrophage cell lines. LF contains the characteristic zinc binding motif of metalloproteases and indirect evidence suggest that this hydrolytic activity is essential for its cytotoxicity. To identify the substrate(s) of LF, we have used the yeast two-hybrid system, employing a LF inactive mutant as bait. This approach has led to the identification of the MAP kinase kinases (MAPKKs) Mek1 and Mek2 as proteins capable of specific interaction with LF. LF cleaves Mek1 and Mek2 within their N-terminus in vitro and in vivo, hydrolyzing a Pro8-Ile9 and a Pro10-Arg11 peptide bond in Mek1 and Mek2 respectively. The removal of the amino terminus of MAPKKs eliminates the "docking site" for the MAPKs ERK1 and ERK2, which become phosphorylated in cultured macrophages following toxin challenge. The possible implications of these findings for the cytolysis of macrophage cells induced by LF are discussed. These results open the way to the design and screening of specific inhibitors of LF.

PMID:
9703991
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk