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KMID : 0545120120220020170
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Journal of Microbiology and Biotechnology
2012 Volume.22 No. 2 p.170 ~ p.175
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Clostridium difficile Toxin A Inhibits the Kinase Activity of Extracellular Signal-Related Kinases 1 and 2 Through Direct Binding
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Seok Heon
Nam Hyo-Jung
Nam Seung-Taek
Kang Jin-Ku
Kim Sung-Kuk
Chang Jong-Soo
Ha Eun-Mi
Park Young-Joo
Kim Ho
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Abstract
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Clostridium difficile toxin A glucosylates Rho family proteins, resulting in actin filament disaggregation and cell rounding in cultured colonocytes. Given that the cellular toxicity of toxin A is dependent on its receptor binding and subsequent entry into the cell, we herein sought to identify additional colonocyte proteins that might bind to toxin A following its internalization. Our results revealed that toxin A interacted with ERK1 and ERK2 in two human colonocyte cell lines (NCM460 and HT29). A GST-pulldown assay also showed that toxin A can directly bind to ERK1 and ERK2. In NCM460 cells exposed to PMA (an ERK1/2 activator), the phosphorylation of ERK1/2 did not affect the interaction between toxin A and ERK1/2. However, an in vitro kinase assay showed that the direct binding of toxin A to ERK1 or ERK2 inhibited their kinase activities. These results suggest a new molecular mechanism for the cellular toxicity seen in cells exposed to toxin A.
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KEYWORD
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Clostridium difficile, toxin A, protein interaction, ERK1/2, cellular toxicity, toxin internalization
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