کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2130901 1086610 2010 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Dimerization drives PDGF receptor endocytosis through a C-terminal hydrophobic motif shared by EGF receptor
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Dimerization drives PDGF receptor endocytosis through a C-terminal hydrophobic motif shared by EGF receptor
چکیده انگلیسی

Like many other receptor tyrosine kinases (RTKs), platelet-derived growth factor (PDGF) receptor β (PDGFR-β) is internalized and degraded in lysosomes in response to PDGF stimulation, which regulates many aspects of cell signalling. However, little is known about the regulation of PDGFR-β endocytosis. Given that ligand binding is essential for the rapid internalization of RTKs, the events induced by the ligand binding likely contribute to the regulation of ligand-induced RTK internalization. These events include receptor dimerization, activation of intrinsic tyrosine kinase activity and autophosphorylation. In this communication, we examined the role of PDGFR-β kinase activity, PDGFR-β dimerization and PDGFR-β C-terminal motifs in PDGF-induced PDGFR-β internalization. We showed that inhibition of PDGFR-β kinase activity by chemical inhibitor or mutation did not block PDGF-induced PDGFR-β endocytosis, suggesting that the kinase activity is not essential. We further showed that dimerization of PDGFR-β is essential and sufficient to drive PDGFR-β internalization independent of PDGFR-β kinase activation. Moreover, we showed that the previously reported 14 amino acid sequence 952–965 is required for PDGF-induced PDGFR-β internalization. Most importantly, we showed that this PDGFR-β internalization motif is exchangeable with the EGFR internalization motif (1005–1017) in mediating ligand-induced internalization of both PDGFR-β and EGFR. This indicates a common mechanism for the internalization of both PDGFR-β and EGFR.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 316, Issue 14, 15 August 2010, Pages 2237–2250
نویسندگان
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