QI-FRET: a new tool in Receptor Tyrosine Kinase research

QI-FRET：受体酪氨酸激酶研究的新工具

• 批准号: 8331783
• 负责人: Kalina Hristova
• 金额: $ 15.71万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8331783
• 关键词: Biological; Cell membrane; Cells; Chinese Hamster Ovary Cell; Dimerization; Disease; Energy Transfer; Fibroblast Growth Factor Receptors; Fluorescence; Fluorescence Resonance Energy Transfer; Free Energy; Genes; Goals; Growth Disorders; Heterodimerization; Homo; Human Pathology; Image; Knowledge; Lateral; Length; Ligands; Link; Maps; Measures; Membrane; Methodology; Methods; Microscope; Pathology; Process; Proteins; Receptor Protein-Tyrosine Kinases; Research; Signal Transduction; Skeletal system; Systems Development; Universities; Vesicle; Work; cancer therapy; dimer; human disease; malignant breast neoplasm; novel; overexpression; protein expression; receptor; research study; tool

DESCRIPTION (provided by applicant): QI-FRET: a new tool in Receptor Tyrosine Kinase research Kalina Hristova, Johns Hopkins University Ligand-independent homo and heterodimerization of receptor tyrosine kinases (RTKs) is a process that is not well understood despite being implicated in various human pathologies. The lack of knowledge is mainly due to a lack of an appropriate methodology to measure the dimerization energetics of full-length RTK. The lack of knowledge is, in turn, a bottleneck in developing effective RTK-targeted therapies. Here we propose to (i) develop a quantitative imaging FRET (QI-FRET) method that yields dimerization free energies in plasma membrane-derived vesicles and to (ii) characterize the homo and heterodimerization free energies of the ErbB and FGF receptors, chosen because of their very strong link to human disease. Upon the completion of this work, we will be able to predict the degree of ligand-independent dimerization, and thus biological activity, as a function of RTK expression. The method that will be established and the knowledge gained will ultimately aid the search and refinement of effective RTK-targeted treatments for cancers and growth disorders.

描述（由申请人提供）：QI-FRET：受体酪氨酸激酶研究的新工具Kalina Hristova，约翰霍普金斯大学受体酪氨酸激酶（RTKs）的配体独立同源和异源二聚化是一个尽管与各种人类病理有关但尚未得到很好理解的过程。缺乏知识主要是由于缺乏适当的方法来测量全长RTK的二聚化能量。缺乏相关知识反过来又成为开发有效的rtk靶向疗法的瓶颈。在这里，我们建议(i)开发一种定量成像FRET （QI-FRET）方法，该方法可以在质膜来源的囊泡中产生二聚化自由能，（ii）表征ErbB和FGF受体的同源和异二聚化自由能，选择ErbB和FGF受体是因为它们与人类疾病有很强的联系。在完成这项工作后，我们将能够预测与配体无关的二聚化程度，从而预测RTK表达的生物活性。将建立的方法和所获得的知识将最终有助于寻找和改进针对癌症和生长障碍的有效rtk靶向治疗方法。