COMPLEX BETWEEN DIFFERENTLY PHOSPHORYLATED KINASE DOMAIN OF FGFR1 AND TAMDEN SH2

FGFR1 和 TAMDEN SH2 不同磷酸化激酶结构域之间的复合物

• 批准号: 7602304
• 负责人: JOSEPH SCHLESSINGER
• 金额: $ 0.41万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7602304
• 关键词: Binding; C-terminal; Complex; Computer Retrieval of Information on Scientific Projects Database; FGFR1 gene; Funding; Grant; Institution; Phosphorylation; Phosphotransferases; Research; Research Personnel; Resources; Signal Pathway; Source; Structure; Tyrosine; United States National Institutes of Health; phospholipase C gamma; src Homology Domains

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Structures of differently phosphorylated kinase domain of FGFR1 will give better understanding of intermediate states of FGFR1 activation. To get more information, I try to co-crystallize activated kinase domain with a natural substrate, a domain construct containing two Src Homology domain (SH2) and C-terminal extension of Phospholipase C gamma (PLCg). This binds to phosphorylated tyrosine 766 (pY766) of kinase and its tyrosine 781 (Y781) on C-terminal extension is phosphorylated by kinase in trans. These structures will bring elucidation of phosphorylation mechanism of FGFR1 and give more opportunities to explore the downstream signaling pathways through binding mode between substrate and kinase.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 FGFR1 不同磷酸化激酶结构域的结构将有助于更好地了解 FGFR1 激活的中间状态。为了获得更多信息，我尝试将活化的激酶结构域与天然底物共结晶，该结构域构建体包含两个 Src 同源结构域 (SH2) 和磷脂酶 C γ (PLCg) 的 C 末端延伸。它与激酶的磷酸化酪氨酸 766 (pY766) 结合，其 C 端延伸上的酪氨酸 781 (Y781) 被激酶反式磷酸化。这些结构将阐明FGFR1的磷酸化机制，并为通过底物与激酶之间的结合模式探索下游信号通路提供更多机会。