کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2042213 1073189 2014 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Complex Relationship between Ligand Binding and Dimerization in the Epidermal Growth Factor Receptor
ترجمه فارسی عنوان
ارتباط پیچیده بین لیگاندهای اتصال و دیمریزاسیون در گیرنده فاکتور رشد اپیدرمال
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
چکیده انگلیسی


• Preformed extracellular dimers of human EGFR are structurally heterogeneous
• EGFR dimerization does not stabilize ligand binding
• Extracellular mutations found in glioblastoma do not stabilize EGFR dimerization
• Glioblastoma mutations in EGFR increase ligand-binding affinity

SummaryThe epidermal growth factor receptor (EGFR) plays pivotal roles in development and is mutated or overexpressed in several cancers. Despite recent advances, the complex allosteric regulation of EGFR remains incompletely understood. Through efforts to understand why the negative cooperativity observed for intact EGFR is lost in studies of its isolated extracellular region (ECR), we uncovered unexpected relationships between ligand binding and receptor dimerization. The two processes appear to compete. Surprisingly, dimerization does not enhance ligand binding (although ligand binding promotes dimerization). We further show that simply forcing EGFR ECRs into preformed dimers without ligand yields ill-defined, heterogeneous structures. Finally, we demonstrate that extracellular EGFR-activating mutations in glioblastoma enhance ligand-binding affinity without directly promoting EGFR dimerization, suggesting that these oncogenic mutations alter the allosteric linkage between dimerization and ligand binding. Our findings have important implications for understanding how EGFR and its relatives are activated by specific ligands and pathological mutations.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 9, Issue 4, 20 November 2014, Pages 1306–1317
نویسندگان
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