Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Clostridium difficile Toxin A Inhibits the Kinase Activity of Extracellular Signal-Related Kinases 1 and 2 Through Direct Binding

  • Seok, Heon (Department of Biomedical Science, Jungwon University) ;
  • Nam, Hyo-Jung (Department of Life Science, College of Natural Science, Daejin University) ;
  • Nam, Seung-Taek (Department of Life Science, College of Natural Science, Daejin University) ;
  • Kang, Jin-Ku (Department of Life Science, College of Natural Science, Daejin University) ;
  • Kim, Sung-Kuk (Department of Life Science, College of Natural Science, Daejin University) ;
  • Chang, Jong-Soo (Department of Life Science, College of Natural Science, Daejin University) ;
  • Ha, Eun-Mi (College of Pharmacy, Catholic University of Daegu) ;
  • Park, Young-Joo (Department of Internal Medicine, Seoul National University College of Medicine) ;
  • Kim, Ho (Department of Life Science, College of Natural Science, Daejin University)
  • Received : 2011.10.25
  • Accepted : 2011.10.27
  • Published : 2012.02.28
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Abstract

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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References

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