Publication Date:
1998-05-23
Description:
Anthrax lethal toxin, produced by the bacterium Bacillus anthracis, is the major cause of death in animals infected with anthrax. One component of this toxin, lethal factor (LF), is suspected to be a metalloprotease, but no physiological substrates have been identified. Here it is shown that LF is a protease that cleaves the amino terminus of mitogen-activated protein kinase kinases 1 and 2 (MAPKK1 and MAPKK2) and that this cleavage inactivates MAPKK1 and inhibits the MAPK signal transduction pathway. The identification of a cleavage site for LF may facilitate the development of LF inhibitors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Duesbery, N S -- Webb, C P -- Leppla, S H -- Gordon, V M -- Klimpel, K R -- Copeland, T D -- Ahn, N G -- Oskarsson, M K -- Fukasawa, K -- Paull, K D -- Vande Woude, G F -- New York, N.Y. -- Science. 1998 May 1;280(5364):734-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Advanced BioScience Laboratories-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Post Office Box B, Frederick, MD 21702.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9563949" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
*Antigens, Bacterial
;
*Bacillus anthracis/enzymology
;
Bacterial Toxins/metabolism/*toxicity
;
Binding Sites
;
Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors/metabolism
;
Cell Line, Transformed
;
Enzyme Activation
;
Enzyme Inhibitors/toxicity
;
Humans
;
MAP Kinase Kinase 1
;
MAP Kinase Kinase 2
;
Metalloendopeptidases/metabolism/toxicity
;
Mice
;
*Mitogen-Activated Protein Kinase Kinases
;
Myelin Basic Protein/metabolism
;
Oocytes/physiology
;
Phosphorylation
;
Protein-Serine-Threonine Kinases/*antagonists &
;
inhibitors/chemistry/genetics/metabolism
;
Protein-Tyrosine Kinases/*antagonists & inhibitors/chemistry/genetics/metabolism
;
Recombinant Fusion Proteins/metabolism
;
Sequence Deletion
;
Signal Transduction
;
Xenopus laevis
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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