Structure Study of Angiopoietins and the Tie2 Receptor

血管生成素和Tie2受体的结构研究

• 批准号: 7475189
• 负责人: DIMITAR B NIKOLOV
• 金额: $ 34.63万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7475189
• 关键词: Address; Adult; Affinity; Agonist; Angiopoietin-1; Angiopoietin-2; Angiopoietins; Binding; Biochemical; Biological; Biological Assay; Blood Vessels; Cell physiology; Cells; Class; Complex; Crystallography; Cytoplasm; Development; Dissociation; Equilibrium; Event; Family; Family member; Fibrinogen; Glycoproteins; Goals; Growth and Development function; Ligand Binding Domain; Ligands; Lymphatic System; Maintenance; Measures; Mediating; Medical; Molecular; Neoplasm Metastasis; Organism; Orphan; Play; Receptor Activation; Receptor Protein-Tyrosine Kinases; Role; Screening procedure; Signal Transduction; Signaling Molecule; Structure; Surface; System; TIE-2 Receptor; Techniques; X-Ray Crystallography; angiogenesis; base; extracellular; in vivo; insight; member; protein function; receptor; receptor binding; research study; tool; tumor growth

DESCRIPTION (provided by applicant): Angiogenesis is a complex cellular process involving the branching, expansion, and maturation of primordial blood vessels into a complex microvasculature. The Angiopoietin/Tie receptor-ligand system plays a central role in these events. The Angiopoietins are secreted molecules that signal through the endothelial specific Tie2 receptor. This is a unique receptor tyrosine kinase signaling system in that distinct Angiopoietin ligands, although highly homologous, may function as agonist or antagonist in a context dependent manner. A detailed understanding of the mechanisms of Angiopoietin-Tie signaling and their function during angiogenesis requires comprehensive structural and biophysical analysis of both the Angiopoietins and the Tie receptors as well as of their interactions. The specific goals of this proposal include: i) structural analysis of the ligand binding domain of at least two Angiopoietin family members, ii) structural analysis of the ligand-binding domain of Tie2 as well as of the equivalent region of the related orphan receptor Tie1, iii) structural analysis of receptor recognition and formation of an Angiopoietin-Tie2 complex and iv) biochemical characterization of Angiopoietin-Tie interactions and receptor activation.

描述（由申请人提供）：血管生成是一种复杂的细胞过程，涉及原始血管的分支，扩张和成熟到复杂的微脉管系统中。血管生成素/TIE受体配体系统在这些事件中起着核心作用。血管生成素是通过内皮特异性TIE2受体发信号的分泌分子。这是一个独特的受体酪氨酸激酶信号系统，因为尽管高度同源，但在上下文中可能是激动剂或拮抗剂。对血管生成蛋白信号传导及其功能的机制的详细理解需要对血管生成蛋白和TIE受体及其相互作用的全面结构和生物物理分析。该提案的具体目标包括：i）至少两个血管生成素家族成员的配体结合结构域的结构分析，ii）TIE2的配体结合域的结构分析以及相关孤儿受体领带的等效区域的结构分析。血管生成素的相互作用和受体激活。