Extracellular proteins are made in the cytosol and transported out of the cell. Certain proteins travel the opposite way, from the outside to the cytosol. Most of these proteins are toxins made by bacteria and plants, but evidence is accumulating that certain growth factors can do the same. Toxins that enter the cytosol can, according to current knowledge, be roughly classified into two main groups, those that enter from endosomes and those that enter from the endoplasmic reticulum (Alouf and Freer 1999). In both cases, the travel to the cytosol is initiated by binding of the toxin to cell surface receptors, followed by endocytosis.

Diphtheria toxin, the protein responsible for the tissue damage in diphtheria, is the most famous and best studied of these toxins. Like many other toxins acting inside cells, the active form consists of...

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