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Uptake and function of anthrax toxins

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-5210891

PubChem

R-HSA-5210891

Description

Bacillus anthracis bacteria target cells in an infected human through the action of three secreted bacterial proteins, lef (also known as LF, lethal factor), cya (also known as EF, edema factor), and pagA (also known as PA, protective antigen) (Turk 2007; Young and Collier 2007). lef is a protease that cleaves and inactivates many MAP2K (MAP kinase kinase, MEK) proteins (Duesbery et al. 1998; Vitale et al. 2000), disrupting MAP kinase signaling pathways. cya is an adenylate cyclase that mediates the constitutive production of cAMP (Leppla 1982), a molecule normally generated transiently in tightly regulated amounts in response to extracellular signals. Both lef and cya depend on pagA to enter their target cells, a strategy characteristic of bacterial binary toxins (Barth et al. 2004). pagA binds to the target cell receptors, is cleaved by furin or other cellular proteases, and thereupon forms an oligomer that exposes binding sites for lef and cya molecules (Young and Collier 2007). This complex is taken into the target cell by clathrin mediated endocytosis and delivered to endosomes. The low pH of the endosome causes the bacterial toxin complex to rearrange: the pagA oligomer forms a pore in the endosome membrane through which lef and cya molecules enter the target cell cytosol.

Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.

SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying **all 5** entries
UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
P09958	Furin	FUR FURIN PACE PCSK3	view
P36507	Dual specificity mitogen-activated protein kinase kinase 2	MAP2K2 MEK2 MKK2 PRKMK2	view
P45985	Dual specificity mitogen-activated protein kinase kinase 4	JNKK1 MAP2K4 MEK4 MKK4 PRKMK4 SEK1 SERK1 SKK1	view
Q02750	Dual specificity mitogen-activated protein kinase kinase 1	MAP2K1 MEK1 PRKMK1	view
Q8WUM4	Programmed cell death 6-interacting protein	AIP1 ALIX KIAA1375 PDCD6IP	view

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