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Cell-Surface Monkey CD9 Antigen is a Coreceptor that Increases Diphtheria Toxin Sensitivity and Diphtheria Toxin Receptor (proHB-EGF) Affinity.

 Jeong-Heon Cha  ;  Joanna S. Brooke  ;  Kathryn N. Ivey  ;  Leon Eidels 
 Journal of Biological Chemistry, Vol.275(10) : 6901-6907, 2000 
Journal Title
 Journal of Biological Chemistry 
Issue Date
Amino Acid Sequence ; Animals ; Antigens, CD/metabolism* ; Cell Line ; Diphtheria Toxin/metabolism ; Diphtheria Toxin/pharmacology* ; Haplorhini ; Heparin-binding EGF-like Growth Factor ; Intercellular Signaling Peptides and Proteins ; Membrane Glycoproteins* ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Protein Precursors/metabolism ; Receptor, Epidermal Growth Factor/metabolism ; Receptors, Cell Surface/metabolism* ; Tetraspanin-29
Monkey (Mk) CD9 antigen has been shown previously to increase the diphtheria toxin (DT) sensitivity of cells when co-expressed with Mk proHB-EGF (DT receptor). We have elucidated here the mechanism whereby Mk CD9 influences Mk proHB-EGF and present evidence that Mk CD9 is a coreceptor for DT. We observed that Mk CD9 not only increased the DT sensitivity but also increased the DT receptor affinity of cells. Furthermore, the higher the Mk CD9/Mk proHB-EGF ratio, the higher the affinity. In contrast, mouse (Ms) CD9 did not increase the toxin sensitivity or receptor affinity of cells when co-expressed with Mk proHB-EGF. Using Mk/Ms chimeric CD9 molecules, we determined that the second extracellular domain of Mk CD9 is responsible for both increased sensitivity and receptor affinity. This domain of Mk CD9 also interacts with Mk proHB-EGF in a yeast two-hybrid system. Our findings thus suggest that Mk CD9 has a direct physical interaction with Mk proHB-EGF to form a DT receptor complex and that this contact may change the conformation of the receptor to increase DT binding affinity and consequently increase toxin sensitivity. We thus propose that Mk CD9 is a coreceptor for DT.
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2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Cha, Jung Heon(차정헌) ORCID logo https://orcid.org/0000-0002-9385-2653
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