scholarly journals The Influence of Furin and the KDEL Receptor on the Efficacy of Recombinant Immunotoxins based on Pseudomonas Exotoxin A

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Yuyi Zhu ◽  
John Weldon
Keyword(s):  
Exotoxin A ◽  
Pseudomonas Exotoxin ◽  
Pseudomonas Exotoxin A ◽  
Recombinant Immunotoxins ◽  
Kdel Receptor

scholarly journals Designing the Furin-Cleavable Linker in Recombinant Immunotoxins Based on Pseudomonas Exotoxin A

2015 ◽  
Vol 26 (6) ◽  
pp. 1120-1128 ◽  
Author(s):  
John E. Weldon ◽  
Martin Skarzynski ◽  
Jamy A. Therres ◽  
Joshua R. Ostovitz ◽  
Hong Zhou ◽  
...  
Keyword(s):  
Exotoxin A ◽  
Pseudomonas Exotoxin ◽  
Pseudomonas Exotoxin A ◽  
Recombinant Immunotoxins

Cytotoxicity of Antiosteosarcoma Recombinant Immunotoxins Composed of TP-3 Fv Fragments and a Truncated Pseudomonas Exotoxin A

2001 ◽  
Vol 24 (2) ◽  
pp. 144-150 ◽  
Author(s):  
Masanori Onda ◽  
Tove Olafsen ◽  
Yasuo Tsutsumi ◽  
Øyvind S. Bruland ◽  
Ira Pastan
Keyword(s):  
Exotoxin A ◽  
Pseudomonas Exotoxin ◽  
Pseudomonas Exotoxin A ◽  
Recombinant Immunotoxins

The KDEL retrieval system is exploited by Pseudomonas exotoxin A, but not by Shiga-like toxin-1, during retrograde transport from the Golgi complex to the endoplasmic reticulum

1999 ◽  
Vol 112 (4) ◽  
pp. 467-475 ◽  
Author(s):  
M.E. Jackson ◽  
J.C. Simpson ◽  
A. Girod ◽  
R. Pepperkok ◽  
L.M. Roberts ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Golgi Complex ◽  
Retrograde Transport ◽  
Vero Cells ◽  
Exotoxin A ◽  
Pseudomonas Exotoxin ◽  
Pseudomonas Exotoxin A ◽  
Protein Toxins ◽  
Kdel Receptor

To investigate the role of the KDEL receptor in the retrieval of protein toxins to the mammalian cell endoplasmic reticulum (ER), lysozyme variants containing AARL or KDEL C-terminal tags, or the human KDEL receptor, have been expressed in toxin-treated COS 7 and HeLa cells. Expression of the lysozyme variants and the KDEL receptor was confirmed by immunofluorescence. When such cells were challenged with diphtheria toxin (DT) or Escherichia coli Shiga-like toxin 1 (SLT-1), there was no observable difference in their sensitivities as compared to cells which did not express these exogenous proteins. By contrast, the cytotoxicity of Pseudomonas exotoxin A (PE) is reduced by expressing lysozyme-KDEL, which causes a redistribution of the KDEL receptor from the Golgi complex to the ER, and cells are sensitised to this toxin when they express additional KDEL receptors. These data suggest that, in contrast to SLT-1, PE can exploit the KDEL receptor in order to reach the ER lumen where it is believed that membrane transfer to the cytosol occurs. This contention was confirmed by microinjecting into Vero cells antibodies raised against the cytoplasmically exposed tail of the KDEL receptor. Immunofluorescence confirmed that these antibodies prevented the retrograde transport of the KDEL receptor from the Golgi complex to the ER, and this in turn reduced the cytotoxicity of PE, but not that of SLT-1, to these cells.

scholarly journals Pseudomonas exotoxin A. Membrane binding, insertion, and traversal.

1986 ◽  
Vol 261 (24) ◽  
pp. 11404-11408 ◽  
Author(s):  
Z T Farahbakhsh ◽  
R L Baldwin ◽  
B J Wisnieski
Keyword(s):  
Membrane Binding ◽  
Exotoxin A ◽  
Pseudomonas Exotoxin ◽  
Pseudomonas Exotoxin A
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