Anthrax lethal factor-cleavage products of MAPK (mitogen-activated protein kinase) kinases exhibit reduced binding to their cognate MAPKs

被引：82

作者：

Bardwell, A. Jane ^{[1
]}

Abdollahi, Mahsa ^{[1
]}

Bardwell, Lee ^{[1
]}

机构：

[1] Dept. of Devmtl. and Cell Biology, 2208 Natural Sciences I, University of California, Irvine

来源：

Biochemical Journal | 2004年 / 378卷 / 02期

关键词：

Anthrax lethal factor protease; Docking site; MAPK kinase (MKK); MAPK/ERK kinase (MEK); Mitogen-activated protein kinase (MAPK); Molecular pathogenesis;

D O I：

10.1042/BJ20031382

中图分类号：

学科分类号：

摘要：

Anthrax lethal toxin is the major cause of death in systemic anthrax. Lethal toxin consists of two proteins: protective antigen and LF (lethal factor). Protective antigen binds to a cell-surface receptor and transports LF into the cytosol. LF is a metalloprotease that targets MKKs [MAPK (mitogen-activated protein kinase) kinases]/MEKs [MAPK/ERK (extracellular- signal-regulated kinase) kinases], cleaving them to remove a small N-terminal stretch but leaving the bulk of the protein, including the protein kinase domain, intact. LF-mediated cleavage of MEK1 and MKK6 has been shown to inhibit signalling through their cognate MAPK pathways. However, the precise mechanism by which this proteolytic cleavage inhibits signal transmission has been unclear. Here we show that the C-terminal LF-cleavage products of MEK1, MEK2, MKK3, MKK4, MKK6 and MKK7 are impaired in their ability to bind to their MAPK substrates, suggesting a common mechanism for the LF-induced inhibition of signalling.

引用

页码：569 / 577

页数：8

共 45 条

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