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Effect of the anti-receptor ligand-blocking 225 monoclonal antibody on EGF receptor endocytosis and sorting

From National Research Council Canada

DOIResolve DOI: https://doi.org/10.1016/j.yexcr.2006.05.008
AuthorSearch for: 1; Search for: 1; Search for: 1; Search for: 1; Search for: 2; Search for: 1
Affiliation
  1. National Research Council of Canada. NRC Biotechnology Research Institute
  2. National Research Council of Canada. NRC Institute for Biological Sciences
FormatText, Article
SubjectMonoclonal-antibody; monoclonal-antibodies; antibody; Antibodies; receptor; epidermal growth factor receptor; endocytosis; internalization; recycling; downregulation; epidermal growth factor; pharmaceutical; tyrosine; biotechnology
Abstract
The anti-receptor antibody, 225 mAb, is known to block binding of ligand to the epidermal growth factor receptor (EGFR). However, the effect of this neutralizing antibody on EGFR endocytosis, trafficking and degradation remains unclear. Here, we demonstrate that endocytosis of ¹²⁵I-225 mAb occurs, albeit with a slower rate than that of EGF. Using pulse chase assays, we show that internalized ¹²⁵I-225 mAb is recycled to the surface much more efficiently than internalized ¹²⁵I-EGF. Also, we found that internalization of ¹²⁵I-225 mAb, in contrast to that of EGF, is independent of receptor tyrosine kinase activity, as evidenced by its insensitivity to AG1478, a specific EGFR tyrosine kinase inhibitor. Analysis of the levels of cell surface and total EGFR showed that treatment with 225 mAb results in a 30–40% decrease in surface EGFR and a relatively slow downregulation of total EGFR. Taken together, these data indicate that 225 mAb induces internalization and downregulation of EGFR via a mechanism distinct from that underlying EGF-induced EGFR internalization and downregulation.
Publication date
In
  • Experimental Cell Research 312, no. 15 (September 2006): 2778–2790.
LanguageEnglish
NRC number47476
JARAMILLO2006
NPARC number9387260
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Record identifier5a3ae4e7-a68f-41d5-8b0a-a807ddc3f561
Record created2009-07-10
Record modified2020-04-22
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