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Papers In Press, published online ahead of print July 1, 2005
Pathology, Anatomy & Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107
Corresponding Author: iozzo{at}mail.jci.tju.edu
Decorin inhibits the epidermal growth factor receptor (EGFR) by down-regulating its tyrosine kinase activity, thereby blocking the growth of a variety of transformed cells and tumor xenografts. In this study we provide evidence that decorin directly binds to the EGFR causing its dimerization, internalization and ultimately its degradation. Using various pharmacological agents to disrupt clathrin-dependent and -independent endocytosis, we demonstrate that decorin evokes a protracted internalization of the EGFR primarily via caveolar-mediated endocytosis. In contrast to EGF, decorin targets the EGFR to caveolae, but not to early or recycling endosomes. Ultimately, however, both EGF- and decorin-induced pathways converge into late endosomes/lysosomes for final degradation. Thus, we have discovered a novel biological mechanism for decorin which could explain its anti-proliferative and anti-oncogenic mode of action.
J. Biol. Chem, 10.1074/jbc.M503833200
Submitted on April 8, 2005
Revised on June 27, 2005
Accepted on July 1, 2005
Decorin evokes protracted internalization and degradation of the EGF receptor via caveolar endocytosis
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