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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 FGFR 1的不同磷酸化激酶结构域的结构将更好地理解FGFR 1激活的中间状态。为了获得更多的信息，我尝试将活化的激酶结构域与天然底物共结晶，所述天然底物是包含两个Src同源结构域（SH 2）和磷脂酶C γ（PLCg）的C末端延伸的结构域构建体。该结构与激酶的磷酸化酪氨酸766（pY 766）结合，其C端延伸的酪氨酸781（Y 781）被激酶反式磷酸化，这些结构将有助于阐明FGFR 1的磷酸化机制，并为通过底物与激酶的结合模式探索下游信号通路提供更多的机会。