Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor.

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Vitale G, Bernardi L, Napolitani G, Mock M, Montecucco C

Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor.

Biochem J. 2000 Dec 15;352 Pt 3:739-45.

PubMed ID
11104681 [ View in PubMed
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Abstract

The lethal factor (LF) produced by toxigenic strains of Bacillus anthracis is a Zn(2+)-endopeptidase that cleaves the mitogen-activated protein kinase kinases (MAPKKs) MEK1, MEK2 and MKK3. Using genetic and biochemical approaches, we have extended the study of LF proteolytic specificity to all known MAPKK family members and found that LF also cleaves MKK4, MKK6 and MKK7, but not MEK5. The peptide bonds hydrolysed by LF within all MAPKKs were identified. Cleavage invariably occurs within the N-terminal proline-rich region preceding the kinase domain, thus disrupting a sequence involved in directing specific protein-protein interactions necessary for the assembly of signalling complexes. Alignment of the sequences flanking the site of cleavage reveals the occurrence of some consensus motifs: position P2 and P1' are occupied by hydrophobic residues and at least one basic residue is present between P4 and P7. The implications of these findings for the biochemical activity and functional specificity of LF are discussed.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Dual specificity mitogen-activated protein kinase kinase 1Q02750Details
Lethal factorP15917Details
Dual specificity mitogen-activated protein kinase kinase 2P36507Details
Dual specificity mitogen-activated protein kinase kinase 6P52564Details
Dual specificity mitogen-activated protein kinase kinase 4P45985Details
Dual specificity mitogen-activated protein kinase kinase 7O14733Details