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

Journal Article · Sun Sep 10 04:00:00 EDT 2006 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2006.05.008· OSTI ID:20858015

Jaramillo, Maria L ^[1]; Leon, Zully ^[1]; Grothe, Suzanne ^[1]; Paul-Roc, Beatrice ^[1]; Abulrob, Abedelnasser ^[2]; O'Connor McCourt, Maureen ^[1]

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1. Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Avenue, Montreal, Quebec, H4P 2R2 (Canada)
2. Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, K1A 0R6 (Canada)

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 {sup 125}I-225 mAb occurs, albeit with a slower rate than that of EGF. Using pulse chase assays, we show that internalized {sup 125}I-225 mAb is recycled to the surface much more efficiently than internalized {sup 125}I-EGF. Also, we found that internalization of {sup 125}I-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.

• OSTI ID: 20858015
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 15 Vol. 312; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ALBUMINS
CATTLE
GROWTH FACTORS
IODINE 125
LEAD SULFIDES
LIGANDS
MONOCLONAL ANTIBODIES
PHOSPHATES
RECEPTORS
TYROSINE