Decorin evokes protracted internalization and degradation of the epidermal growth factor receptor via caveolar endocytosis. Export

@article{citeulike:367072, abstract = {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 that could explain its anti-proliferative and anti-oncogenic mode of action.}, address = {Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.}, author = {Zhu, J. X. and Goldoni, S. and Bix, G. and Owens, R. T. and McQuillan, D. J. and Reed, C. C. and Iozzo, R. V.}, citeulike-article-id = {367072}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M503833200}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15994311}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15994311}, day = {16}, doi = {10.1074/jbc.M503833200}, issn = {0021-9258}, journal = {J Biol Chem}, keywords = {caveolae, egfr, endocytosis}, month = {September}, number = {37}, pages = {32468--32479}, posted-at = {2005-10-27 17:54:47}, priority = {2}, title = {Decorin evokes protracted internalization and degradation of the epidermal growth factor receptor via caveolar endocytosis.}, url = {http://dx.doi.org/10.1074/jbc.M503833200}, volume = {280}, year = {2005} }

TY - JOUR ID - citeulike:367072 L3 - citeulike-article-id:367072 N2 - 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 that could explain its anti-proliferative and anti-oncogenic mode of action. IS - 37 JF - J Biol Chem SN - 0021-9258 AD - Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. EP - 32479 TI - Decorin evokes protracted internalization and degradation of the epidermal growth factor receptor via caveolar endocytosis. VL - 280 SP - 32468 KW - caveolae KW - egfr KW - endocytosis AU - Zhu, JX AU - Goldoni, S AU - Bix, G AU - Owens, RT AU - McQuillan, DJ AU - Reed, CC AU - Iozzo, RV PY - 2005/09/16/ UR - http://dx.doi.org/10.1074/jbc.M503833200 ER -