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Anthrax lethal factor causes proteolytic inactivation of mitogen‐activated protein kinase kinase
Author(s) -
Duesbery N. S.,
Woude G. F. Vande
Publication year - 1999
Publication title -
journal of applied microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.889
H-Index - 156
eISSN - 1365-2672
pISSN - 1364-5072
DOI - 10.1046/j.1365-2672.1999.00892.x
Subject(s) - protein kinase a , mitogen activated protein kinase kinase , microbiology and biotechnology , mitogen activated protein kinase , protein kinase r , kinase , biology , chemistry
A search of the National Cancer Institute’s Anti‐Neoplastic Drug Screen for compounds with an inhibitory profile similar to that of the mitogen‐activated protein kinase kinase (MAPKK) inhibitor PD098059 yielded anthrax lethal toxin. Anthrax lethal factor was found to inhibit progesterone‐induced meiotic maturation of frog oocytes by preventing the phosphorylation and activation of mitogen‐activated protein kinase (MAPK). Similarly, lethal toxin prevented the activation of MAPK in serum stimulated, ras‐transformed NIH3T3 cells. In vitro analyses using recombinant proteins indicated that lethal factor proteolytically modified the NH 2 ‐terminus of both MAPKK1 and 2, rendering them inactive and hence incapable of activating MAPK. The consequences of this inactivation upon meiosis and transformed cells are also discussed.